VCV000438942.17 - ClinVar

NM_007294.4(BRCA1):c.5529_5530delinsCA (p.Leu1844Ile)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(5)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(4); Likely benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_007294.4(BRCA1):c.5529_5530delinsCA (p.Leu1844Ile)

Variation ID: 438942 Accession: VCV000438942.17

Type and length

Indel, 2 bp

Location

Cytogenetic: 17q21.31 17: 43045740-43045741 (GRCh38) [ NCBI UCSC ] 17: 41197757-41197758 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Sep 30, 2017	May 1, 2024	Jan 18, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_007294.4:c.5529_5530delinsCA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_009225.1:p.Leu1844Ile	missense
NM_001407571.1:c.5316_5317delACinsCA	NP_001394500.1:p.Leu1773Ile	missense
NM_001407581.1:c.5595_5596delACinsCA	NP_001394510.1:p.Leu1866Ile	missense
NM_001407582.1:c.5595_5596delACinsCA	NP_001394511.1:p.Leu1866Ile	missense
NM_001407583.1:c.5592_5593delACinsCA	NP_001394512.1:p.Leu1865Ile	missense
NM_001407585.1:c.5592_5593delACinsCA	NP_001394514.1:p.Leu1865Ile	missense
NM_001407587.1:c.5592_5593delACinsCA	NP_001394516.1:p.Leu1865Ile	missense
NM_001407590.1:c.5589_5590delACinsCA	NP_001394519.1:p.Leu1864Ile	missense
NM_001407591.1:c.5589_5590delACinsCA	NP_001394520.1:p.Leu1864Ile	missense
NM_001407593.1:c.5529_5530delACinsCA	NP_001394522.1:p.Leu1844Ile	missense
NM_001407594.1:c.5529_5530delACinsCA	NP_001394523.1:p.Leu1844Ile	missense
NM_001407596.1:c.5529_5530delACinsCA	NP_001394525.1:p.Leu1844Ile	missense
NM_001407597.1:c.5529_5530delACinsCA	NP_001394526.1:p.Leu1844Ile	missense
NM_001407598.1:c.5529_5530delACinsCA	NP_001394527.1:p.Leu1844Ile	missense
NM_001407602.1:c.5529_5530delACinsCA	NP_001394531.1:p.Leu1844Ile	missense
NM_001407603.1:c.5529_5530delACinsCA	NP_001394532.1:p.Leu1844Ile	missense
NM_001407605.1:c.5529_5530delACinsCA	NP_001394534.1:p.Leu1844Ile	missense
NM_001407610.1:c.5526_5527delACinsCA	NP_001394539.1:p.Leu1843Ile	missense
NM_001407611.1:c.5526_5527delACinsCA	NP_001394540.1:p.Leu1843Ile	missense
NM_001407612.1:c.5526_5527delACinsCA	NP_001394541.1:p.Leu1843Ile	missense
NM_001407613.1:c.5526_5527delACinsCA	NP_001394542.1:p.Leu1843Ile	missense
NM_001407614.1:c.5526_5527delACinsCA	NP_001394543.1:p.Leu1843Ile	missense
NM_001407615.1:c.5526_5527delACinsCA	NP_001394544.1:p.Leu1843Ile	missense
NM_001407616.1:c.5526_5527delACinsCA	NP_001394545.1:p.Leu1843Ile	missense
NM_001407617.1:c.5526_5527delACinsCA	NP_001394546.1:p.Leu1843Ile	missense
NM_001407618.1:c.5526_5527delACinsCA	NP_001394547.1:p.Leu1843Ile	missense
NM_001407619.1:c.5526_5527delACinsCA	NP_001394548.1:p.Leu1843Ile	missense
NM_001407620.1:c.5526_5527delACinsCA	NP_001394549.1:p.Leu1843Ile	missense
NM_001407621.1:c.5526_5527delACinsCA	NP_001394550.1:p.Leu1843Ile	missense
NM_001407622.1:c.5526_5527delACinsCA	NP_001394551.1:p.Leu1843Ile	missense
NM_001407623.1:c.5526_5527delACinsCA	NP_001394552.1:p.Leu1843Ile	missense
NM_001407624.1:c.5526_5527delACinsCA	NP_001394553.1:p.Leu1843Ile	missense
NM_001407625.1:c.5526_5527delACinsCA	NP_001394554.1:p.Leu1843Ile	missense
NM_001407626.1:c.5526_5527delACinsCA	NP_001394555.1:p.Leu1843Ile	missense
NM_001407627.1:c.5523_5524delACinsCA	NP_001394556.1:p.Leu1842Ile	missense
NM_001407628.1:c.5523_5524delACinsCA	NP_001394557.1:p.Leu1842Ile	missense
NM_001407629.1:c.5523_5524delACinsCA	NP_001394558.1:p.Leu1842Ile	missense
NM_001407630.1:c.5523_5524delACinsCA	NP_001394559.1:p.Leu1842Ile	missense
NM_001407631.1:c.5523_5524delACinsCA	NP_001394560.1:p.Leu1842Ile	missense
NM_001407632.1:c.5523_5524delACinsCA	NP_001394561.1:p.Leu1842Ile	missense
NM_001407633.1:c.5523_5524delACinsCA	NP_001394562.1:p.Leu1842Ile	missense
NM_001407634.1:c.5523_5524delACinsCA	NP_001394563.1:p.Leu1842Ile	missense
NM_001407635.1:c.5523_5524delACinsCA	NP_001394564.1:p.Leu1842Ile	missense
NM_001407636.1:c.5523_5524delACinsCA	NP_001394565.1:p.Leu1842Ile	missense
NM_001407637.1:c.5523_5524delACinsCA	NP_001394566.1:p.Leu1842Ile	missense
NM_001407638.1:c.5523_5524delACinsCA	NP_001394567.1:p.Leu1842Ile	missense
NM_001407639.1:c.5523_5524delACinsCA	NP_001394568.1:p.Leu1842Ile	missense
NM_001407640.1:c.5523_5524delACinsCA	NP_001394569.1:p.Leu1842Ile	missense
NM_001407641.1:c.5523_5524delACinsCA	NP_001394570.1:p.Leu1842Ile	missense
NM_001407642.1:c.5523_5524delACinsCA	NP_001394571.1:p.Leu1842Ile	missense
NM_001407644.1:c.5520_5521delACinsCA	NP_001394573.1:p.Leu1841Ile	missense
NM_001407645.1:c.5520_5521delACinsCA	NP_001394574.1:p.Leu1841Ile	missense
NM_001407646.1:c.5517_5518delACinsCA	NP_001394575.1:p.Leu1840Ile	missense
NM_001407647.1:c.5514_5515delACinsCA	NP_001394576.1:p.Leu1839Ile	missense
NM_001407648.1:c.5472_5473delACinsCA	NP_001394577.1:p.Leu1825Ile	missense
NM_001407649.1:c.5469_5470delACinsCA	NP_001394578.1:p.Leu1824Ile	missense
NM_001407652.1:c.5451_5452delACinsCA	NP_001394581.1:p.Leu1818Ile	missense
NM_001407653.1:c.5451_5452delACinsCA	NP_001394582.1:p.Leu1818Ile	missense
NM_001407654.1:c.5451_5452delACinsCA	NP_001394583.1:p.Leu1818Ile	missense
NM_001407655.1:c.5451_5452delACinsCA	NP_001394584.1:p.Leu1818Ile	missense
NM_001407656.1:c.5448_5449delACinsCA	NP_001394585.1:p.Leu1817Ile	missense
NM_001407657.1:c.5448_5449delACinsCA	NP_001394586.1:p.Leu1817Ile	missense
NM_001407658.1:c.5448_5449delACinsCA	NP_001394587.1:p.Leu1817Ile	missense
NM_001407659.1:c.5445_5446delACinsCA	NP_001394588.1:p.Leu1816Ile	missense
NM_001407660.1:c.5445_5446delACinsCA	NP_001394589.1:p.Leu1816Ile	missense
NM_001407661.1:c.5445_5446delACinsCA	NP_001394590.1:p.Leu1816Ile	missense
NM_001407662.1:c.5445_5446delACinsCA	NP_001394591.1:p.Leu1816Ile	missense
NM_001407663.1:c.5445_5446delACinsCA	NP_001394592.1:p.Leu1816Ile	missense
NM_001407664.1:c.5406_5407delACinsCA	NP_001394593.1:p.Leu1803Ile	missense
NM_001407665.1:c.5406_5407delACinsCA	NP_001394594.1:p.Leu1803Ile	missense
NM_001407666.1:c.5406_5407delACinsCA	NP_001394595.1:p.Leu1803Ile	missense
NM_001407667.1:c.5406_5407delACinsCA	NP_001394596.1:p.Leu1803Ile	missense
NM_001407668.1:c.5406_5407delACinsCA	NP_001394597.1:p.Leu1803Ile	missense
NM_001407669.1:c.5406_5407delACinsCA	NP_001394598.1:p.Leu1803Ile	missense
NM_001407670.1:c.5403_5404delACinsCA	NP_001394599.1:p.Leu1802Ile	missense
NM_001407671.1:c.5403_5404delACinsCA	NP_001394600.1:p.Leu1802Ile	missense
NM_001407672.1:c.5403_5404delACinsCA	NP_001394601.1:p.Leu1802Ile	missense
NM_001407673.1:c.5403_5404delACinsCA	NP_001394602.1:p.Leu1802Ile	missense
NM_001407674.1:c.5403_5404delACinsCA	NP_001394603.1:p.Leu1802Ile	missense
NM_001407675.1:c.5403_5404delACinsCA	NP_001394604.1:p.Leu1802Ile	missense
NM_001407676.1:c.5403_5404delACinsCA	NP_001394605.1:p.Leu1802Ile	missense
NM_001407677.1:c.5403_5404delACinsCA	NP_001394606.1:p.Leu1802Ile	missense
NM_001407678.1:c.5403_5404delACinsCA	NP_001394607.1:p.Leu1802Ile	missense
NM_001407679.1:c.5403_5404delACinsCA	NP_001394608.1:p.Leu1802Ile	missense
NM_001407680.1:c.5403_5404delACinsCA	NP_001394609.1:p.Leu1802Ile	missense
NM_001407681.1:c.5400_5401delACinsCA	NP_001394610.1:p.Leu1801Ile	missense
NM_001407682.1:c.5400_5401delACinsCA	NP_001394611.1:p.Leu1801Ile	missense
NM_001407683.1:c.5400_5401delACinsCA	NP_001394612.1:p.Leu1801Ile	missense
NM_001407684.1:c.5400_5401delACinsCA	NP_001394613.1:p.Leu1801Ile	missense
NM_001407685.1:c.5400_5401delACinsCA	NP_001394614.1:p.Leu1801Ile	missense
NM_001407686.1:c.5400_5401delACinsCA	NP_001394615.1:p.Leu1801Ile	missense
NM_001407687.1:c.5400_5401delACinsCA	NP_001394616.1:p.Leu1801Ile	missense
NM_001407688.1:c.5400_5401delACinsCA	NP_001394617.1:p.Leu1801Ile	missense
NM_001407689.1:c.5400_5401delACinsCA	NP_001394618.1:p.Leu1801Ile	missense
NM_001407690.1:c.5397_5398delACinsCA	NP_001394619.1:p.Leu1800Ile	missense
NM_001407691.1:c.5397_5398delACinsCA	NP_001394620.1:p.Leu1800Ile	missense
NM_001407692.1:c.5388_5389delACinsCA	NP_001394621.1:p.Leu1797Ile	missense
NM_001407694.1:c.5388_5389delACinsCA	NP_001394623.1:p.Leu1797Ile	missense
NM_001407695.1:c.5388_5389delACinsCA	NP_001394624.1:p.Leu1797Ile	missense
NM_001407696.1:c.5388_5389delACinsCA	NP_001394625.1:p.Leu1797Ile	missense
NM_001407697.1:c.5388_5389delACinsCA	NP_001394626.1:p.Leu1797Ile	missense
NM_001407698.1:c.5388_5389delACinsCA	NP_001394627.1:p.Leu1797Ile	missense
NM_001407724.1:c.5388_5389delACinsCA	NP_001394653.1:p.Leu1797Ile	missense
NM_001407725.1:c.5388_5389delACinsCA	NP_001394654.1:p.Leu1797Ile	missense
NM_001407726.1:c.5388_5389delACinsCA	NP_001394655.1:p.Leu1797Ile	missense
NM_001407727.1:c.5388_5389delACinsCA	NP_001394656.1:p.Leu1797Ile	missense
NM_001407728.1:c.5388_5389delACinsCA	NP_001394657.1:p.Leu1797Ile	missense
NM_001407729.1:c.5388_5389delACinsCA	NP_001394658.1:p.Leu1797Ile	missense
NM_001407730.1:c.5388_5389delACinsCA	NP_001394659.1:p.Leu1797Ile	missense
NM_001407731.1:c.5388_5389delACinsCA	NP_001394660.1:p.Leu1797Ile	missense
NM_001407732.1:c.5385_5386delACinsCA	NP_001394661.1:p.Leu1796Ile	missense
NM_001407733.1:c.5385_5386delACinsCA	NP_001394662.1:p.Leu1796Ile	missense
NM_001407734.1:c.5385_5386delACinsCA	NP_001394663.1:p.Leu1796Ile	missense
NM_001407735.1:c.5385_5386delACinsCA	NP_001394664.1:p.Leu1796Ile	missense
NM_001407736.1:c.5385_5386delACinsCA	NP_001394665.1:p.Leu1796Ile	missense
NM_001407737.1:c.5385_5386delACinsCA	NP_001394666.1:p.Leu1796Ile	missense
NM_001407738.1:c.5385_5386delACinsCA	NP_001394667.1:p.Leu1796Ile	missense
NM_001407739.1:c.5385_5386delACinsCA	NP_001394668.1:p.Leu1796Ile	missense
NM_001407740.1:c.5385_5386delACinsCA	NP_001394669.1:p.Leu1796Ile	missense
NM_001407741.1:c.5385_5386delACinsCA	NP_001394670.1:p.Leu1796Ile	missense
NM_001407742.1:c.5385_5386delACinsCA	NP_001394671.1:p.Leu1796Ile	missense
NM_001407743.1:c.5385_5386delACinsCA	NP_001394672.1:p.Leu1796Ile	missense
NM_001407744.1:c.5385_5386delACinsCA	NP_001394673.1:p.Leu1796Ile	missense
NM_001407745.1:c.5385_5386delACinsCA	NP_001394674.1:p.Leu1796Ile	missense
NM_001407746.1:c.5385_5386delACinsCA	NP_001394675.1:p.Leu1796Ile	missense
NM_001407747.1:c.5385_5386delACinsCA	NP_001394676.1:p.Leu1796Ile	missense
NM_001407748.1:c.5385_5386delACinsCA	NP_001394677.1:p.Leu1796Ile	missense
NM_001407749.1:c.5385_5386delACinsCA	NP_001394678.1:p.Leu1796Ile	missense
NM_001407750.1:c.5385_5386delACinsCA	NP_001394679.1:p.Leu1796Ile	missense
NM_001407751.1:c.5385_5386delACinsCA	NP_001394680.1:p.Leu1796Ile	missense
NM_001407752.1:c.5385_5386delACinsCA	NP_001394681.1:p.Leu1796Ile	missense
NM_001407838.1:c.5382_5383delACinsCA	NP_001394767.1:p.Leu1795Ile	missense
NM_001407839.1:c.5382_5383delACinsCA	NP_001394768.1:p.Leu1795Ile	missense
NM_001407841.1:c.5382_5383delACinsCA	NP_001394770.1:p.Leu1795Ile	missense
NM_001407842.1:c.5382_5383delACinsCA	NP_001394771.1:p.Leu1795Ile	missense
NM_001407843.1:c.5382_5383delACinsCA	NP_001394772.1:p.Leu1795Ile	missense
NM_001407844.1:c.5382_5383delACinsCA	NP_001394773.1:p.Leu1795Ile	missense
NM_001407845.1:c.5382_5383delACinsCA	NP_001394774.1:p.Leu1795Ile	missense
NM_001407846.1:c.5382_5383delACinsCA	NP_001394775.1:p.Leu1795Ile	missense
NM_001407847.1:c.5382_5383delACinsCA	NP_001394776.1:p.Leu1795Ile	missense
NM_001407848.1:c.5382_5383delACinsCA	NP_001394777.1:p.Leu1795Ile	missense
NM_001407849.1:c.5382_5383delACinsCA	NP_001394778.1:p.Leu1795Ile	missense
NM_001407850.1:c.5382_5383delACinsCA	NP_001394779.1:p.Leu1795Ile	missense
NM_001407851.1:c.5382_5383delACinsCA	NP_001394780.1:p.Leu1795Ile	missense
NM_001407852.1:c.5382_5383delACinsCA	NP_001394781.1:p.Leu1795Ile	missense
NM_001407853.1:c.5382_5383delACinsCA	NP_001394782.1:p.Leu1795Ile	missense
NM_001407854.1:c.43_44delACinsCA
NM_001407858.1:c.43_44delACinsCA
NM_001407859.1:c.43_44delACinsCA
NM_001407860.1:c.43_44delACinsCA
NM_001407861.1:c.43_44delACinsCA
NM_001407862.1:c.5328_5329delACinsCA	NP_001394791.1:p.Leu1777Ile	missense
NM_001407863.1:c.5325_5326delACinsCA	NP_001394792.1:p.Leu1776Ile	missense
NM_001407874.1:c.5322_5323delACinsCA	NP_001394803.1:p.Leu1775Ile	missense
NM_001407875.1:c.5322_5323delACinsCA	NP_001394804.1:p.Leu1775Ile	missense
NM_001407879.1:c.5319_5320delACinsCA	NP_001394808.1:p.Leu1774Ile	missense
NM_001407881.1:c.5319_5320delACinsCA	NP_001394810.1:p.Leu1774Ile	missense
NM_001407882.1:c.5319_5320delACinsCA	NP_001394811.1:p.Leu1774Ile	missense
NM_001407884.1:c.5319_5320delACinsCA	NP_001394813.1:p.Leu1774Ile	missense
NM_001407885.1:c.5319_5320delACinsCA	NP_001394814.1:p.Leu1774Ile	missense
NM_001407886.1:c.5319_5320delACinsCA	NP_001394815.1:p.Leu1774Ile	missense
NM_001407887.1:c.5319_5320delACinsCA	NP_001394816.1:p.Leu1774Ile	missense
NM_001407889.1:c.5319_5320delACinsCA	NP_001394818.1:p.Leu1774Ile	missense
NM_001407894.1:c.5316_5317delACinsCA	NP_001394823.1:p.Leu1773Ile	missense
NM_001407895.1:c.5316_5317delACinsCA	NP_001394824.1:p.Leu1773Ile	missense
NM_001407896.1:c.5316_5317delACinsCA	NP_001394825.1:p.Leu1773Ile	missense
NM_001407897.1:c.5316_5317delACinsCA	NP_001394826.1:p.Leu1773Ile	missense
NM_001407898.1:c.5316_5317delACinsCA	NP_001394827.1:p.Leu1773Ile	missense
NM_001407899.1:c.5316_5317delACinsCA	NP_001394828.1:p.Leu1773Ile	missense
NM_001407900.1:c.5316_5317delACinsCA	NP_001394829.1:p.Leu1773Ile	missense
NM_001407902.1:c.5316_5317delACinsCA	NP_001394831.1:p.Leu1773Ile	missense
NM_001407904.1:c.5316_5317delACinsCA	NP_001394833.1:p.Leu1773Ile	missense
NM_001407906.1:c.5316_5317delACinsCA	NP_001394835.1:p.Leu1773Ile	missense
NM_001407907.1:c.5316_5317delACinsCA	NP_001394836.1:p.Leu1773Ile	missense
NM_001407908.1:c.5316_5317delACinsCA	NP_001394837.1:p.Leu1773Ile	missense
NM_001407909.1:c.5316_5317delACinsCA	NP_001394838.1:p.Leu1773Ile	missense
NM_001407910.1:c.5316_5317delACinsCA	NP_001394839.1:p.Leu1773Ile	missense
NM_001407915.1:c.5313_5314delACinsCA	NP_001394844.1:p.Leu1772Ile	missense
NM_001407916.1:c.5313_5314delACinsCA	NP_001394845.1:p.Leu1772Ile	missense
NM_001407917.1:c.5313_5314delACinsCA	NP_001394846.1:p.Leu1772Ile	missense
NM_001407918.1:c.5313_5314delACinsCA	NP_001394847.1:p.Leu1772Ile	missense
NM_001407919.1:c.5277_5278delACinsCA	NP_001394848.1:p.Leu1760Ile	missense
NM_001407920.1:c.5265_5266delACinsCA	NP_001394849.1:p.Leu1756Ile	missense
NM_001407921.1:c.5265_5266delACinsCA	NP_001394850.1:p.Leu1756Ile	missense
NM_001407922.1:c.5265_5266delACinsCA	NP_001394851.1:p.Leu1756Ile	missense
NM_001407923.1:c.5265_5266delACinsCA	NP_001394852.1:p.Leu1756Ile	missense
NM_001407924.1:c.5265_5266delACinsCA	NP_001394853.1:p.Leu1756Ile	missense
NM_001407925.1:c.5265_5266delACinsCA	NP_001394854.1:p.Leu1756Ile	missense
NM_001407926.1:c.5265_5266delACinsCA	NP_001394855.1:p.Leu1756Ile	missense
NM_001407927.1:c.5262_5263delACinsCA	NP_001394856.1:p.Leu1755Ile	missense
NM_001407928.1:c.5262_5263delACinsCA	NP_001394857.1:p.Leu1755Ile	missense
NM_001407929.1:c.5262_5263delACinsCA	NP_001394858.1:p.Leu1755Ile	missense
NM_001407930.1:c.5262_5263delACinsCA	NP_001394859.1:p.Leu1755Ile	missense
NM_001407931.1:c.5262_5263delACinsCA	NP_001394860.1:p.Leu1755Ile	missense
NM_001407932.1:c.5262_5263delACinsCA	NP_001394861.1:p.Leu1755Ile	missense
NM_001407933.1:c.5262_5263delACinsCA	NP_001394862.1:p.Leu1755Ile	missense
NM_001407934.1:c.5259_5260delACinsCA	NP_001394863.1:p.Leu1754Ile	missense
NM_001407935.1:c.5259_5260delACinsCA	NP_001394864.1:p.Leu1754Ile	missense
NM_001407936.1:c.5259_5260delACinsCA	NP_001394865.1:p.Leu1754Ile	missense
NM_001407937.1:c.43_44delACinsCA
NM_001407938.1:c.43_44delACinsCA
NM_001407939.1:c.43_44delACinsCA
NM_001407940.1:c.43_44delACinsCA
NM_001407941.1:c.43_44delACinsCA
NM_001407942.1:c.43_44delACinsCA
NM_001407943.1:c.43_44delACinsCA
NM_001407944.1:c.43_44delACinsCA
NM_001407945.1:c.43_44delACinsCA
NM_001407946.1:c.5196_5197delACinsCA	NP_001394875.1:p.Leu1733Ile	missense
NM_001407947.1:c.5196_5197delACinsCA	NP_001394876.1:p.Leu1733Ile	missense
NM_001407948.1:c.5196_5197delACinsCA	NP_001394877.1:p.Leu1733Ile	missense
NM_001407949.1:c.5196_5197delACinsCA	NP_001394878.1:p.Leu1733Ile	missense
NM_001407950.1:c.5193_5194delACinsCA	NP_001394879.1:p.Leu1732Ile	missense
NM_001407951.1:c.5193_5194delACinsCA	NP_001394880.1:p.Leu1732Ile	missense
NM_001407952.1:c.5193_5194delACinsCA	NP_001394881.1:p.Leu1732Ile	missense
NM_001407953.1:c.5193_5194delACinsCA	NP_001394882.1:p.Leu1732Ile	missense
NM_001407954.1:c.5193_5194delACinsCA	NP_001394883.1:p.Leu1732Ile	missense
NM_001407955.1:c.5193_5194delACinsCA	NP_001394884.1:p.Leu1732Ile	missense
NM_001407956.1:c.5190_5191delACinsCA	NP_001394885.1:p.Leu1731Ile	missense
NM_001407957.1:c.5190_5191delACinsCA	NP_001394886.1:p.Leu1731Ile	missense
NM_001407958.1:c.5190_5191delACinsCA	NP_001394887.1:p.Leu1731Ile	missense
NM_001407959.1:c.5148_5149delACinsCA	NP_001394888.1:p.Leu1717Ile	missense
NM_001407960.1:c.5145_5146delACinsCA	NP_001394889.1:p.Leu1716Ile	missense
NM_001407962.1:c.5145_5146delACinsCA	NP_001394891.1:p.Leu1716Ile	missense
NM_001407963.1:c.5142_5143delACinsCA	NP_001394892.1:p.Leu1715Ile	missense
NM_001407964.1:c.5067_5068delACinsCA	NP_001394893.1:p.Leu1690Ile	missense
NM_001407965.1:c.5022_5023delACinsCA	NP_001394894.1:p.Leu1675Ile	missense
NM_001407966.1:c.4641_4642delACinsCA	NP_001394895.1:p.Leu1548Ile	missense
NM_001407967.1:c.4638_4639delACinsCA	NP_001394896.1:p.Leu1547Ile	missense
NM_001407968.1:c.2925_2926delACinsCA	NP_001394897.1:p.Leu976Ile	missense
NM_001407969.1:c.2922_2923delACinsCA	NP_001394898.1:p.Leu975Ile	missense
NM_001407970.1:c.2286_2287delACinsCA	NP_001394899.1:p.Leu763Ile	missense
NM_001407971.1:c.2286_2287delACinsCA	NP_001394900.1:p.Leu763Ile	missense
NM_001407972.1:c.2283_2284delACinsCA	NP_001394901.1:p.Leu762Ile	missense
NM_001407973.1:c.2220_2221delACinsCA	NP_001394902.1:p.Leu741Ile	missense
NM_001407974.1:c.2220_2221delACinsCA	NP_001394903.1:p.Leu741Ile	missense
NM_001407975.1:c.2220_2221delACinsCA	NP_001394904.1:p.Leu741Ile	missense
NM_001407976.1:c.2220_2221delACinsCA	NP_001394905.1:p.Leu741Ile	missense
NM_001407977.1:c.2220_2221delACinsCA	NP_001394906.1:p.Leu741Ile	missense
NM_001407978.1:c.2220_2221delACinsCA	NP_001394907.1:p.Leu741Ile	missense
NM_001407979.1:c.2217_2218delACinsCA	NP_001394908.1:p.Leu740Ile	missense
NM_001407980.1:c.2217_2218delACinsCA	NP_001394909.1:p.Leu740Ile	missense
NM_001407981.1:c.2217_2218delACinsCA	NP_001394910.1:p.Leu740Ile	missense
NM_001407982.1:c.2217_2218delACinsCA	NP_001394911.1:p.Leu740Ile	missense
NM_001407983.1:c.2217_2218delACinsCA	NP_001394912.1:p.Leu740Ile	missense
NM_001407984.1:c.2217_2218delACinsCA	NP_001394913.1:p.Leu740Ile	missense
NM_001407985.1:c.2217_2218delACinsCA	NP_001394914.1:p.Leu740Ile	missense
NM_001407986.1:c.2217_2218delACinsCA	NP_001394915.1:p.Leu740Ile	missense
NM_001407990.1:c.2217_2218delACinsCA	NP_001394919.1:p.Leu740Ile	missense
NM_001407991.1:c.2217_2218delACinsCA	NP_001394920.1:p.Leu740Ile	missense
NM_001407992.1:c.2217_2218delACinsCA	NP_001394921.1:p.Leu740Ile	missense
NM_001407993.1:c.2217_2218delACinsCA	NP_001394922.1:p.Leu740Ile	missense
NM_001408392.1:c.2214_2215delACinsCA	NP_001395321.1:p.Leu739Ile	missense
NM_001408396.1:c.2214_2215delACinsCA	NP_001395325.1:p.Leu739Ile	missense
NM_001408397.1:c.2214_2215delACinsCA	NP_001395326.1:p.Leu739Ile	missense
NM_001408398.1:c.2214_2215delACinsCA	NP_001395327.1:p.Leu739Ile	missense
NM_001408399.1:c.2214_2215delACinsCA	NP_001395328.1:p.Leu739Ile	missense
NM_001408400.1:c.2214_2215delACinsCA	NP_001395329.1:p.Leu739Ile	missense
NM_001408401.1:c.2214_2215delACinsCA	NP_001395330.1:p.Leu739Ile	missense
NM_001408402.1:c.2214_2215delACinsCA	NP_001395331.1:p.Leu739Ile	missense
NM_001408403.1:c.2214_2215delACinsCA	NP_001395332.1:p.Leu739Ile	missense
NM_001408404.1:c.2214_2215delACinsCA	NP_001395333.1:p.Leu739Ile	missense
NM_001408406.1:c.2211_2212delACinsCA	NP_001395335.1:p.Leu738Ile	missense
NM_001408407.1:c.2211_2212delACinsCA	NP_001395336.1:p.Leu738Ile	missense
NM_001408408.1:c.2211_2212delACinsCA	NP_001395337.1:p.Leu738Ile	missense
NM_001408409.1:c.2208_2209delACinsCA	NP_001395338.1:p.Leu737Ile	missense
NM_001408410.1:c.2145_2146delACinsCA	NP_001395339.1:p.Leu716Ile	missense
NM_001408411.1:c.2142_2143delACinsCA	NP_001395340.1:p.Leu715Ile	missense
NM_001408412.1:c.2139_2140delACinsCA	NP_001395341.1:p.Leu714Ile	missense
NM_001408413.1:c.2139_2140delACinsCA	NP_001395342.1:p.Leu714Ile	missense
NM_001408414.1:c.2139_2140delACinsCA	NP_001395343.1:p.Leu714Ile	missense
NM_001408415.1:c.2139_2140delACinsCA	NP_001395344.1:p.Leu714Ile	missense
NM_001408416.1:c.2139_2140delACinsCA	NP_001395345.1:p.Leu714Ile	missense
NM_001408418.1:c.2103_2104delACinsCA	NP_001395347.1:p.Leu702Ile	missense
NM_001408419.1:c.2103_2104delACinsCA	NP_001395348.1:p.Leu702Ile	missense
NM_001408420.1:c.2103_2104delACinsCA	NP_001395349.1:p.Leu702Ile	missense
NM_001408421.1:c.2100_2101delACinsCA	NP_001395350.1:p.Leu701Ile	missense
NM_001408422.1:c.2100_2101delACinsCA	NP_001395351.1:p.Leu701Ile	missense
NM_001408423.1:c.2100_2101delACinsCA	NP_001395352.1:p.Leu701Ile	missense
NM_001408424.1:c.2100_2101delACinsCA	NP_001395353.1:p.Leu701Ile	missense
NM_001408425.1:c.2097_2098delACinsCA	NP_001395354.1:p.Leu700Ile	missense
NM_001408426.1:c.2097_2098delACinsCA	NP_001395355.1:p.Leu700Ile	missense
NM_001408427.1:c.2097_2098delACinsCA	NP_001395356.1:p.Leu700Ile	missense
NM_001408428.1:c.2097_2098delACinsCA	NP_001395357.1:p.Leu700Ile	missense
NM_001408429.1:c.2097_2098delACinsCA	NP_001395358.1:p.Leu700Ile	missense
NM_001408430.1:c.2097_2098delACinsCA	NP_001395359.1:p.Leu700Ile	missense
NM_001408431.1:c.2097_2098delACinsCA	NP_001395360.1:p.Leu700Ile	missense
NM_001408432.1:c.2094_2095delACinsCA	NP_001395361.1:p.Leu699Ile	missense
NM_001408433.1:c.2094_2095delACinsCA	NP_001395362.1:p.Leu699Ile	missense
NM_001408434.1:c.2094_2095delACinsCA	NP_001395363.1:p.Leu699Ile	missense
NM_001408435.1:c.2094_2095delACinsCA	NP_001395364.1:p.Leu699Ile	missense
NM_001408436.1:c.2094_2095delACinsCA	NP_001395365.1:p.Leu699Ile	missense
NM_001408437.1:c.2094_2095delACinsCA	NP_001395366.1:p.Leu699Ile	missense
NM_001408438.1:c.2094_2095delACinsCA	NP_001395367.1:p.Leu699Ile	missense
NM_001408439.1:c.2094_2095delACinsCA	NP_001395368.1:p.Leu699Ile	missense
NM_001408440.1:c.2094_2095delACinsCA	NP_001395369.1:p.Leu699Ile	missense
NM_001408441.1:c.2094_2095delACinsCA	NP_001395370.1:p.Leu699Ile	missense
NM_001408442.1:c.2094_2095delACinsCA	NP_001395371.1:p.Leu699Ile	missense
NM_001408443.1:c.2094_2095delACinsCA	NP_001395372.1:p.Leu699Ile	missense
NM_001408444.1:c.2094_2095delACinsCA	NP_001395373.1:p.Leu699Ile	missense
NM_001408445.1:c.2091_2092delACinsCA	NP_001395374.1:p.Leu698Ile	missense
NM_001408446.1:c.2091_2092delACinsCA	NP_001395375.1:p.Leu698Ile	missense
NM_001408447.1:c.2091_2092delACinsCA	NP_001395376.1:p.Leu698Ile	missense
NM_001408448.1:c.2091_2092delACinsCA	NP_001395377.1:p.Leu698Ile	missense
NM_001408450.1:c.2091_2092delACinsCA	NP_001395379.1:p.Leu698Ile	missense
NM_001408451.1:c.2085_2086delACinsCA	NP_001395380.1:p.Leu696Ile	missense
NM_001408452.1:c.2079_2080delACinsCA	NP_001395381.1:p.Leu694Ile	missense
NM_001408453.1:c.2079_2080delACinsCA	NP_001395382.1:p.Leu694Ile	missense
NM_001408454.1:c.2079_2080delACinsCA	NP_001395383.1:p.Leu694Ile	missense
NM_001408455.1:c.2079_2080delACinsCA	NP_001395384.1:p.Leu694Ile	missense
NM_001408456.1:c.2079_2080delACinsCA	NP_001395385.1:p.Leu694Ile	missense
NM_001408457.1:c.2079_2080delACinsCA	NP_001395386.1:p.Leu694Ile	missense
NM_001408458.1:c.2076_2077delACinsCA	NP_001395387.1:p.Leu693Ile	missense
NM_001408459.1:c.2076_2077delACinsCA	NP_001395388.1:p.Leu693Ile	missense
NM_001408460.1:c.2076_2077delACinsCA	NP_001395389.1:p.Leu693Ile	missense
NM_001408461.1:c.2076_2077delACinsCA	NP_001395390.1:p.Leu693Ile	missense
NM_001408462.1:c.2076_2077delACinsCA	NP_001395391.1:p.Leu693Ile	missense
NM_001408463.1:c.2076_2077delACinsCA	NP_001395392.1:p.Leu693Ile	missense
NM_001408464.1:c.2076_2077delACinsCA	NP_001395393.1:p.Leu693Ile	missense
NM_001408465.1:c.2076_2077delACinsCA	NP_001395394.1:p.Leu693Ile	missense
NM_001408466.1:c.2076_2077delACinsCA	NP_001395395.1:p.Leu693Ile	missense
NM_001408467.1:c.2076_2077delACinsCA	NP_001395396.1:p.Leu693Ile	missense
NM_001408468.1:c.2073_2074delACinsCA	NP_001395397.1:p.Leu692Ile	missense
NM_001408469.1:c.2073_2074delACinsCA	NP_001395398.1:p.Leu692Ile	missense
NM_001408470.1:c.2073_2074delACinsCA	NP_001395399.1:p.Leu692Ile	missense
NM_001408472.1:c.43_44delACinsCA
NM_001408473.1:c.43_44delACinsCA
NM_001408474.1:c.2019_2020delACinsCA	NP_001395403.1:p.Leu674Ile	missense
NM_001408475.1:c.2016_2017delACinsCA	NP_001395404.1:p.Leu673Ile	missense
NM_001408476.1:c.2016_2017delACinsCA	NP_001395405.1:p.Leu673Ile	missense
NM_001408478.1:c.2010_2011delACinsCA	NP_001395407.1:p.Leu671Ile	missense
NM_001408479.1:c.2010_2011delACinsCA	NP_001395408.1:p.Leu671Ile	missense
NM_001408480.1:c.2010_2011delACinsCA	NP_001395409.1:p.Leu671Ile	missense
NM_001408481.1:c.2007_2008delACinsCA	NP_001395410.1:p.Leu670Ile	missense
NM_001408482.1:c.2007_2008delACinsCA	NP_001395411.1:p.Leu670Ile	missense
NM_001408483.1:c.2007_2008delACinsCA	NP_001395412.1:p.Leu670Ile	missense
NM_001408484.1:c.2007_2008delACinsCA	NP_001395413.1:p.Leu670Ile	missense
NM_001408485.1:c.2007_2008delACinsCA	NP_001395414.1:p.Leu670Ile	missense
NM_001408489.1:c.2007_2008delACinsCA	NP_001395418.1:p.Leu670Ile	missense
NM_001408490.1:c.2007_2008delACinsCA	NP_001395419.1:p.Leu670Ile	missense
NM_001408491.1:c.2007_2008delACinsCA	NP_001395420.1:p.Leu670Ile	missense
NM_001408492.1:c.2004_2005delACinsCA	NP_001395421.1:p.Leu669Ile	missense
NM_001408493.1:c.2004_2005delACinsCA	NP_001395422.1:p.Leu669Ile	missense
NM_001408494.1:c.1980_1981delACinsCA	NP_001395423.1:p.Leu661Ile	missense
NM_001408495.1:c.1974_1975delACinsCA	NP_001395424.1:p.Leu659Ile	missense
NM_001408496.1:c.1956_1957delACinsCA	NP_001395425.1:p.Leu653Ile	missense
NM_001408497.1:c.1956_1957delACinsCA	NP_001395426.1:p.Leu653Ile	missense
NM_001408498.1:c.1956_1957delACinsCA	NP_001395427.1:p.Leu653Ile	missense
NM_001408499.1:c.1956_1957delACinsCA	NP_001395428.1:p.Leu653Ile	missense
NM_001408500.1:c.1956_1957delACinsCA	NP_001395429.1:p.Leu653Ile	missense
NM_001408501.1:c.1956_1957delACinsCA	NP_001395430.1:p.Leu653Ile	missense
NM_001408502.1:c.1953_1954delACinsCA	NP_001395431.1:p.Leu652Ile	missense
NM_001408503.1:c.1953_1954delACinsCA	NP_001395432.1:p.Leu652Ile	missense
NM_001408504.1:c.1953_1954delACinsCA	NP_001395433.1:p.Leu652Ile	missense
NM_001408505.1:c.1950_1951delACinsCA	NP_001395434.1:p.Leu651Ile	missense
NM_001408506.1:c.1893_1894delACinsCA	NP_001395435.1:p.Leu632Ile	missense
NM_001408507.1:c.1890_1891delACinsCA	NP_001395436.1:p.Leu631Ile	missense
NM_001408508.1:c.1881_1882delACinsCA	NP_001395437.1:p.Leu628Ile	missense
NM_001408509.1:c.1878_1879delACinsCA	NP_001395438.1:p.Leu627Ile	missense
NM_001408510.1:c.1839_1840delACinsCA	NP_001395439.1:p.Leu614Ile	missense
NM_001408511.1:c.1836_1837delACinsCA	NP_001395440.1:p.Leu613Ile	missense
NM_001408512.1:c.1716_1717delACinsCA	NP_001395441.1:p.Leu573Ile	missense
NM_001408513.1:c.1689_1690delACinsCA	NP_001395442.1:p.Leu564Ile	missense
NM_001408514.1:c.1293_1294delACinsCA	NP_001395443.1:p.Leu432Ile	missense
NM_007297.4:c.5388_5389delinsCA	NP_009228.2:p.Leu1797Ile	missense
NM_007298.4:c.2217_2218delACinsCA	NP_009229.2:p.Leu740Ile	missense
NM_007299.4:c.43_44delinsCA		3 prime UTR
NM_007300.4:c.5592_5593delinsCA	NP_009231.2:p.Leu1865Ile	missense
NM_007304.2:c.2217_2218delACinsCA	NP_009235.2:p.Leu740Ile	missense
NR_027676.2:n.5706_5707delinsCA		non-coding transcript variant
NC_000017.11:g.43045740_43045741delinsTG
NC_000017.10:g.41197757_41197758delinsTG
NG_005905.2:g.172243_172244delinsCA
LRG_292:g.172243_172244delinsCA
LRG_292t1:c.5529_5530delACinsCA	LRG_292p1:p.Leu1844Ile

... more HGVS ... less HGVS

Protein change

L1865I, L1797I, L1844I, L740I, L1717I, L1755I, L1776I, L1795I, L1801I, L1816I, L1825I, L432I, L627I, L628I, L669I, L674I, L696I, L699I, L700I, L714I, L737I, L741I, L1548I, L1715I, L1731I, L1733I, L1754I, L1760I, L1775I, L1796I, L1800I, L1802I, L1818I, L1840I, L1841I, L1843I, L564I, L573I, L614I, L651I, L670I, L693I, L694I, L698I, L702I, L715I, L738I, L1547I, L1675I, L1732I, L1756I, L1772I, L1773I, L1774I, L1817I, L1866I, L613I, L631I, L661I, L671I, L673I, L716I, L975I, L1690I, L1716I, L1777I, L1803I, L1824I, L1839I, L1842I, L1864I, L632I, L652I, L653I, L659I, L692I, L701I, L739I, L762I, L763I, L976I

Other names

Canonical SPDI

NC_000017.11:43045739:GT:TG

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA645509524 dbSNP: rs1555574389 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
BRCA1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	13044	14850

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Jan 27, 2022	RCV000505867.11
Hereditary cancer-predisposing syndrome	Conflicting interpretations of pathogenicity (2)	criteria provided, conflicting classifications	Jul 15, 2022	RCV000579620.15
Hereditary breast ovarian cancer syndrome	Uncertain significance (1)	criteria provided, single submitter	Jan 18, 2024	RCV001242747.15

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Apr 23, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000683332.3 First in ClinVar: Feb 19, 2018 Last updated: Jun 22, 2020
Uncertain significance (Mar 25, 2017)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV000600427.2 First in ClinVar: Sep 30, 2017 Last updated: Jan 01, 2022
Uncertain significance (Jan 27, 2022)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000699269.2 First in ClinVar: Mar 17, 2018 Last updated: Feb 13, 2022	Publications: PubMed (2) PubMed: 26689913‚ 30209399 Comment: Variant summary: BRCA1 c.5529_5530delinsCA (p.Leu1844Ile) results in a conservative amino acid change located in the BRCT domain of the encoded protein sequence. Four of five … (more) Variant summary: BRCA1 c.5529_5530delinsCA (p.Leu1844Ile) results in a conservative amino acid change located in the BRCT domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 31394 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5529_5530delinsCA in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome has been reported. One functional study reported experimental evidence evaluating an impact on protein function and showed a different nucleotide change (c.5530C>A) resulting in the same amino acid change results in no damaging effect of this variant on homology directed repair (HDR) activity (e.g. Findlay_2018). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
Uncertain significance (Jan 18, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001415855.5 First in ClinVar: Jul 16, 2020 Last updated: Feb 20, 2024	Publications: PubMed (1) PubMed: 30209399 Comment: This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1844 of the BRCA1 protein (p.Leu1844Ile). … (more) This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1844 of the BRCA1 protein (p.Leu1844Ile). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 438942). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
Likely benign (Jul 15, 2022)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002648716.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Publications: PubMed (1) PubMed: 30209399 Comment: This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more) This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)

Comment:

Variant summary: BRCA1 c.5529_5530delinsCA (p.Leu1844Ile) results in a conservative amino acid change located in the BRCT domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 31394 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5529_5530delinsCA in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome has been reported. One functional study reported experimental evidence evaluating an impact on protein function and showed a different nucleotide change (c.5530C>A) resulting in the same amino acid change results in no damaging effect of this variant on homology directed repair (HDR) activity (e.g. Findlay_2018). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

Comment:

This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1844 of the BRCA1 protein (p.Leu1844Ile). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 438942). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Accurate classification of BRCA1 variants with saturation genome editing.	Findlay GM	Nature	2018	PMID: 30209399
Patterns and functional implications of rare germline variants across 12 cancer types.	Lu C	Nature communications	2015	PMID: 26689913

Text-mined citations for rs1555574389 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 10, 2024

ClinVar Genomic variation as it relates to human health

NM_007294.4(BRCA1):c.5529_5530delinsCA (p.Leu1844Ile)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1555574389 ...