In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The phenylalanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. This sequence change replaces leucine with phenylalanine at codon 1547 of the BRCA1 protein (p.Leu1547Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4641G>T (p.Leu1547Phe)
Germline
Classification
Help
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.
(1)
Help
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.
Uncertain significance
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.4641G>T (p.Leu1547Phe)
Variation ID: 219819 Accession: VCV000219819.8
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43074365 (GRCh38) [ NCBI UCSC ] 17: 41226382 (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 Feb 2, 2016 Feb 28, 2024 Dec 7, 2016 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4641G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Leu1547Phe missense NM_001407571.1:c.4428G>T NP_001394500.1:p.Leu1476Phe missense NM_001407581.1:c.4707G>T NP_001394510.1:p.Leu1569Phe missense NM_001407582.1:c.4707G>T NP_001394511.1:p.Leu1569Phe missense NM_001407583.1:c.4704G>T NP_001394512.1:p.Leu1568Phe missense NM_001407585.1:c.4704G>T NP_001394514.1:p.Leu1568Phe missense NM_001407587.1:c.4704G>T NP_001394516.1:p.Leu1568Phe missense NM_001407590.1:c.4701G>T NP_001394519.1:p.Leu1567Phe missense NM_001407591.1:c.4701G>T NP_001394520.1:p.Leu1567Phe missense NM_001407593.1:c.4641G>T NP_001394522.1:p.Leu1547Phe missense NM_001407594.1:c.4641G>T NP_001394523.1:p.Leu1547Phe missense NM_001407596.1:c.4641G>T NP_001394525.1:p.Leu1547Phe missense NM_001407597.1:c.4641G>T NP_001394526.1:p.Leu1547Phe missense NM_001407598.1:c.4641G>T NP_001394527.1:p.Leu1547Phe missense NM_001407602.1:c.4641G>T NP_001394531.1:p.Leu1547Phe missense NM_001407603.1:c.4641G>T NP_001394532.1:p.Leu1547Phe missense NM_001407605.1:c.4641G>T NP_001394534.1:p.Leu1547Phe missense NM_001407610.1:c.4638G>T NP_001394539.1:p.Leu1546Phe missense NM_001407611.1:c.4638G>T NP_001394540.1:p.Leu1546Phe missense NM_001407612.1:c.4638G>T NP_001394541.1:p.Leu1546Phe missense NM_001407613.1:c.4638G>T NP_001394542.1:p.Leu1546Phe missense NM_001407614.1:c.4638G>T NP_001394543.1:p.Leu1546Phe missense NM_001407615.1:c.4638G>T NP_001394544.1:p.Leu1546Phe missense NM_001407616.1:c.4638G>T NP_001394545.1:p.Leu1546Phe missense NM_001407617.1:c.4638G>T NP_001394546.1:p.Leu1546Phe missense NM_001407618.1:c.4638G>T NP_001394547.1:p.Leu1546Phe missense NM_001407619.1:c.4638G>T NP_001394548.1:p.Leu1546Phe missense NM_001407620.1:c.4638G>T NP_001394549.1:p.Leu1546Phe missense NM_001407621.1:c.4638G>T NP_001394550.1:p.Leu1546Phe missense NM_001407622.1:c.4638G>T NP_001394551.1:p.Leu1546Phe missense NM_001407623.1:c.4638G>T NP_001394552.1:p.Leu1546Phe missense NM_001407624.1:c.4638G>T NP_001394553.1:p.Leu1546Phe missense NM_001407625.1:c.4638G>T NP_001394554.1:p.Leu1546Phe missense NM_001407626.1:c.4638G>T NP_001394555.1:p.Leu1546Phe missense NM_001407627.1:c.4635G>T NP_001394556.1:p.Leu1545Phe missense NM_001407628.1:c.4635G>T NP_001394557.1:p.Leu1545Phe missense NM_001407629.1:c.4635G>T NP_001394558.1:p.Leu1545Phe missense NM_001407630.1:c.4635G>T NP_001394559.1:p.Leu1545Phe missense NM_001407631.1:c.4635G>T NP_001394560.1:p.Leu1545Phe missense NM_001407632.1:c.4635G>T NP_001394561.1:p.Leu1545Phe missense NM_001407633.1:c.4635G>T NP_001394562.1:p.Leu1545Phe missense NM_001407634.1:c.4635G>T NP_001394563.1:p.Leu1545Phe missense NM_001407635.1:c.4635G>T NP_001394564.1:p.Leu1545Phe missense NM_001407636.1:c.4635G>T NP_001394565.1:p.Leu1545Phe missense NM_001407637.1:c.4635G>T NP_001394566.1:p.Leu1545Phe missense NM_001407638.1:c.4635G>T NP_001394567.1:p.Leu1545Phe missense NM_001407639.1:c.4635G>T NP_001394568.1:p.Leu1545Phe missense NM_001407640.1:c.4635G>T NP_001394569.1:p.Leu1545Phe missense NM_001407641.1:c.4635G>T NP_001394570.1:p.Leu1545Phe missense NM_001407642.1:c.4635G>T NP_001394571.1:p.Leu1545Phe missense NM_001407644.1:c.4632G>T NP_001394573.1:p.Leu1544Phe missense NM_001407645.1:c.4632G>T NP_001394574.1:p.Leu1544Phe missense NM_001407646.1:c.4629G>T NP_001394575.1:p.Leu1543Phe missense NM_001407647.1:c.4626G>T NP_001394576.1:p.Leu1542Phe missense NM_001407648.1:c.4584G>T NP_001394577.1:p.Leu1528Phe missense NM_001407649.1:c.4581G>T NP_001394578.1:p.Leu1527Phe missense NM_001407652.1:c.4641G>T NP_001394581.1:p.Leu1547Phe missense NM_001407653.1:c.4563G>T NP_001394582.1:p.Leu1521Phe missense NM_001407654.1:c.4563G>T NP_001394583.1:p.Leu1521Phe missense NM_001407655.1:c.4563G>T NP_001394584.1:p.Leu1521Phe missense NM_001407656.1:c.4560G>T NP_001394585.1:p.Leu1520Phe missense NM_001407657.1:c.4560G>T NP_001394586.1:p.Leu1520Phe missense NM_001407658.1:c.4560G>T NP_001394587.1:p.Leu1520Phe missense NM_001407659.1:c.4557G>T NP_001394588.1:p.Leu1519Phe missense NM_001407660.1:c.4557G>T NP_001394589.1:p.Leu1519Phe missense NM_001407661.1:c.4557G>T NP_001394590.1:p.Leu1519Phe missense NM_001407662.1:c.4557G>T NP_001394591.1:p.Leu1519Phe missense NM_001407663.1:c.4557G>T NP_001394592.1:p.Leu1519Phe missense NM_001407664.1:c.4518G>T NP_001394593.1:p.Leu1506Phe missense NM_001407665.1:c.4518G>T NP_001394594.1:p.Leu1506Phe missense NM_001407666.1:c.4518G>T NP_001394595.1:p.Leu1506Phe missense NM_001407667.1:c.4518G>T NP_001394596.1:p.Leu1506Phe missense NM_001407668.1:c.4518G>T NP_001394597.1:p.Leu1506Phe missense NM_001407669.1:c.4518G>T NP_001394598.1:p.Leu1506Phe missense NM_001407670.1:c.4515G>T NP_001394599.1:p.Leu1505Phe missense NM_001407671.1:c.4515G>T NP_001394600.1:p.Leu1505Phe missense NM_001407672.1:c.4515G>T NP_001394601.1:p.Leu1505Phe missense NM_001407673.1:c.4515G>T NP_001394602.1:p.Leu1505Phe missense NM_001407674.1:c.4515G>T NP_001394603.1:p.Leu1505Phe missense NM_001407675.1:c.4515G>T NP_001394604.1:p.Leu1505Phe missense NM_001407676.1:c.4515G>T NP_001394605.1:p.Leu1505Phe missense NM_001407677.1:c.4515G>T NP_001394606.1:p.Leu1505Phe missense NM_001407678.1:c.4515G>T NP_001394607.1:p.Leu1505Phe missense NM_001407679.1:c.4515G>T NP_001394608.1:p.Leu1505Phe missense NM_001407680.1:c.4515G>T NP_001394609.1:p.Leu1505Phe missense NM_001407681.1:c.4512G>T NP_001394610.1:p.Leu1504Phe missense NM_001407682.1:c.4512G>T NP_001394611.1:p.Leu1504Phe missense NM_001407683.1:c.4512G>T NP_001394612.1:p.Leu1504Phe missense NM_001407684.1:c.4641G>T NP_001394613.1:p.Leu1547Phe missense NM_001407685.1:c.4512G>T NP_001394614.1:p.Leu1504Phe missense NM_001407686.1:c.4512G>T NP_001394615.1:p.Leu1504Phe missense NM_001407687.1:c.4512G>T NP_001394616.1:p.Leu1504Phe missense NM_001407688.1:c.4512G>T NP_001394617.1:p.Leu1504Phe missense NM_001407689.1:c.4512G>T NP_001394618.1:p.Leu1504Phe missense NM_001407690.1:c.4509G>T NP_001394619.1:p.Leu1503Phe missense NM_001407691.1:c.4509G>T NP_001394620.1:p.Leu1503Phe missense NM_001407692.1:c.4500G>T NP_001394621.1:p.Leu1500Phe missense NM_001407694.1:c.4500G>T NP_001394623.1:p.Leu1500Phe missense NM_001407695.1:c.4500G>T NP_001394624.1:p.Leu1500Phe missense NM_001407696.1:c.4500G>T NP_001394625.1:p.Leu1500Phe missense NM_001407697.1:c.4500G>T NP_001394626.1:p.Leu1500Phe missense NM_001407698.1:c.4500G>T NP_001394627.1:p.Leu1500Phe missense NM_001407724.1:c.4500G>T NP_001394653.1:p.Leu1500Phe missense NM_001407725.1:c.4500G>T NP_001394654.1:p.Leu1500Phe missense NM_001407726.1:c.4500G>T NP_001394655.1:p.Leu1500Phe missense NM_001407727.1:c.4500G>T NP_001394656.1:p.Leu1500Phe missense NM_001407728.1:c.4500G>T NP_001394657.1:p.Leu1500Phe missense NM_001407729.1:c.4500G>T NP_001394658.1:p.Leu1500Phe missense NM_001407730.1:c.4500G>T NP_001394659.1:p.Leu1500Phe missense NM_001407731.1:c.4500G>T NP_001394660.1:p.Leu1500Phe missense NM_001407732.1:c.4497G>T NP_001394661.1:p.Leu1499Phe missense NM_001407733.1:c.4497G>T NP_001394662.1:p.Leu1499Phe missense NM_001407734.1:c.4497G>T NP_001394663.1:p.Leu1499Phe missense NM_001407735.1:c.4497G>T NP_001394664.1:p.Leu1499Phe missense NM_001407736.1:c.4497G>T NP_001394665.1:p.Leu1499Phe missense NM_001407737.1:c.4497G>T NP_001394666.1:p.Leu1499Phe missense NM_001407738.1:c.4497G>T NP_001394667.1:p.Leu1499Phe missense NM_001407739.1:c.4497G>T NP_001394668.1:p.Leu1499Phe missense NM_001407740.1:c.4497G>T NP_001394669.1:p.Leu1499Phe missense NM_001407741.1:c.4497G>T NP_001394670.1:p.Leu1499Phe missense NM_001407742.1:c.4497G>T NP_001394671.1:p.Leu1499Phe missense NM_001407743.1:c.4497G>T NP_001394672.1:p.Leu1499Phe missense NM_001407744.1:c.4497G>T NP_001394673.1:p.Leu1499Phe missense NM_001407745.1:c.4497G>T NP_001394674.1:p.Leu1499Phe missense NM_001407746.1:c.4497G>T NP_001394675.1:p.Leu1499Phe missense NM_001407747.1:c.4497G>T NP_001394676.1:p.Leu1499Phe missense NM_001407748.1:c.4497G>T NP_001394677.1:p.Leu1499Phe missense NM_001407749.1:c.4497G>T NP_001394678.1:p.Leu1499Phe missense NM_001407750.1:c.4497G>T NP_001394679.1:p.Leu1499Phe missense NM_001407751.1:c.4497G>T NP_001394680.1:p.Leu1499Phe missense NM_001407752.1:c.4497G>T NP_001394681.1:p.Leu1499Phe missense NM_001407838.1:c.4494G>T NP_001394767.1:p.Leu1498Phe missense NM_001407839.1:c.4494G>T NP_001394768.1:p.Leu1498Phe missense NM_001407841.1:c.4494G>T NP_001394770.1:p.Leu1498Phe missense NM_001407842.1:c.4494G>T NP_001394771.1:p.Leu1498Phe missense NM_001407843.1:c.4494G>T NP_001394772.1:p.Leu1498Phe missense NM_001407844.1:c.4494G>T NP_001394773.1:p.Leu1498Phe missense NM_001407845.1:c.4494G>T NP_001394774.1:p.Leu1498Phe missense NM_001407846.1:c.4494G>T NP_001394775.1:p.Leu1498Phe missense NM_001407847.1:c.4494G>T NP_001394776.1:p.Leu1498Phe missense NM_001407848.1:c.4494G>T NP_001394777.1:p.Leu1498Phe missense NM_001407849.1:c.4494G>T NP_001394778.1:p.Leu1498Phe missense NM_001407850.1:c.4494G>T NP_001394779.1:p.Leu1498Phe missense NM_001407851.1:c.4494G>T NP_001394780.1:p.Leu1498Phe missense NM_001407852.1:c.4494G>T NP_001394781.1:p.Leu1498Phe missense NM_001407853.1:c.4494G>T NP_001394782.1:p.Leu1498Phe missense NM_001407854.1:c.4641G>T NP_001394783.1:p.Leu1547Phe missense NM_001407858.1:c.4638G>T NP_001394787.1:p.Leu1546Phe missense NM_001407859.1:c.4638G>T NP_001394788.1:p.Leu1546Phe missense NM_001407860.1:c.4638G>T NP_001394789.1:p.Leu1546Phe missense NM_001407861.1:c.4635G>T NP_001394790.1:p.Leu1545Phe missense NM_001407862.1:c.4440G>T NP_001394791.1:p.Leu1480Phe missense NM_001407863.1:c.4515G>T NP_001394792.1:p.Leu1505Phe missense NM_001407874.1:c.4434G>T NP_001394803.1:p.Leu1478Phe missense NM_001407875.1:c.4434G>T NP_001394804.1:p.Leu1478Phe missense NM_001407879.1:c.4431G>T NP_001394808.1:p.Leu1477Phe missense NM_001407881.1:c.4431G>T NP_001394810.1:p.Leu1477Phe missense NM_001407882.1:c.4431G>T NP_001394811.1:p.Leu1477Phe missense NM_001407884.1:c.4431G>T NP_001394813.1:p.Leu1477Phe missense NM_001407885.1:c.4431G>T NP_001394814.1:p.Leu1477Phe missense NM_001407886.1:c.4431G>T NP_001394815.1:p.Leu1477Phe missense NM_001407887.1:c.4431G>T NP_001394816.1:p.Leu1477Phe missense NM_001407889.1:c.4431G>T NP_001394818.1:p.Leu1477Phe missense NM_001407894.1:c.4428G>T NP_001394823.1:p.Leu1476Phe missense NM_001407895.1:c.4428G>T NP_001394824.1:p.Leu1476Phe missense NM_001407896.1:c.4428G>T NP_001394825.1:p.Leu1476Phe missense NM_001407897.1:c.4428G>T NP_001394826.1:p.Leu1476Phe missense NM_001407898.1:c.4428G>T NP_001394827.1:p.Leu1476Phe missense NM_001407899.1:c.4428G>T NP_001394828.1:p.Leu1476Phe missense NM_001407900.1:c.4428G>T NP_001394829.1:p.Leu1476Phe missense NM_001407902.1:c.4428G>T NP_001394831.1:p.Leu1476Phe missense NM_001407904.1:c.4428G>T NP_001394833.1:p.Leu1476Phe missense NM_001407906.1:c.4428G>T NP_001394835.1:p.Leu1476Phe missense NM_001407907.1:c.4428G>T NP_001394836.1:p.Leu1476Phe missense NM_001407908.1:c.4428G>T NP_001394837.1:p.Leu1476Phe missense NM_001407909.1:c.4428G>T NP_001394838.1:p.Leu1476Phe missense NM_001407910.1:c.4428G>T NP_001394839.1:p.Leu1476Phe missense NM_001407915.1:c.4425G>T NP_001394844.1:p.Leu1475Phe missense NM_001407916.1:c.4425G>T NP_001394845.1:p.Leu1475Phe missense NM_001407917.1:c.4425G>T NP_001394846.1:p.Leu1475Phe missense NM_001407918.1:c.4425G>T NP_001394847.1:p.Leu1475Phe missense NM_001407919.1:c.4518G>T NP_001394848.1:p.Leu1506Phe missense NM_001407920.1:c.4377G>T NP_001394849.1:p.Leu1459Phe missense NM_001407921.1:c.4377G>T NP_001394850.1:p.Leu1459Phe missense NM_001407922.1:c.4377G>T NP_001394851.1:p.Leu1459Phe missense NM_001407923.1:c.4377G>T NP_001394852.1:p.Leu1459Phe missense NM_001407924.1:c.4377G>T NP_001394853.1:p.Leu1459Phe missense NM_001407925.1:c.4377G>T NP_001394854.1:p.Leu1459Phe missense NM_001407926.1:c.4377G>T NP_001394855.1:p.Leu1459Phe missense NM_001407927.1:c.4374G>T NP_001394856.1:p.Leu1458Phe missense NM_001407928.1:c.4374G>T NP_001394857.1:p.Leu1458Phe missense NM_001407929.1:c.4374G>T NP_001394858.1:p.Leu1458Phe missense NM_001407930.1:c.4374G>T NP_001394859.1:p.Leu1458Phe missense NM_001407931.1:c.4374G>T NP_001394860.1:p.Leu1458Phe missense NM_001407932.1:c.4374G>T NP_001394861.1:p.Leu1458Phe missense NM_001407933.1:c.4374G>T NP_001394862.1:p.Leu1458Phe missense NM_001407934.1:c.4371G>T NP_001394863.1:p.Leu1457Phe missense NM_001407935.1:c.4371G>T NP_001394864.1:p.Leu1457Phe missense NM_001407936.1:c.4371G>T NP_001394865.1:p.Leu1457Phe missense NM_001407937.1:c.4518G>T NP_001394866.1:p.Leu1506Phe missense NM_001407938.1:c.4518G>T NP_001394867.1:p.Leu1506Phe missense NM_001407939.1:c.4515G>T NP_001394868.1:p.Leu1505Phe missense NM_001407940.1:c.4515G>T NP_001394869.1:p.Leu1505Phe missense NM_001407941.1:c.4512G>T NP_001394870.1:p.Leu1504Phe missense NM_001407942.1:c.4500G>T NP_001394871.1:p.Leu1500Phe missense NM_001407943.1:c.4497G>T NP_001394872.1:p.Leu1499Phe missense NM_001407944.1:c.4497G>T NP_001394873.1:p.Leu1499Phe missense NM_001407945.1:c.4497G>T NP_001394874.1:p.Leu1499Phe missense NM_001407946.1:c.4308G>T NP_001394875.1:p.Leu1436Phe missense NM_001407947.1:c.4308G>T NP_001394876.1:p.Leu1436Phe missense NM_001407948.1:c.4308G>T NP_001394877.1:p.Leu1436Phe missense NM_001407949.1:c.4308G>T NP_001394878.1:p.Leu1436Phe missense NM_001407950.1:c.4305G>T NP_001394879.1:p.Leu1435Phe missense NM_001407951.1:c.4305G>T NP_001394880.1:p.Leu1435Phe missense NM_001407952.1:c.4305G>T NP_001394881.1:p.Leu1435Phe missense NM_001407953.1:c.4305G>T NP_001394882.1:p.Leu1435Phe missense NM_001407954.1:c.4305G>T NP_001394883.1:p.Leu1435Phe missense NM_001407955.1:c.4305G>T NP_001394884.1:p.Leu1435Phe missense NM_001407956.1:c.4302G>T NP_001394885.1:p.Leu1434Phe missense NM_001407957.1:c.4302G>T NP_001394886.1:p.Leu1434Phe missense NM_001407958.1:c.4302G>T NP_001394887.1:p.Leu1434Phe missense NM_001407959.1:c.4260G>T NP_001394888.1:p.Leu1420Phe missense NM_001407960.1:c.4257G>T NP_001394889.1:p.Leu1419Phe missense NM_001407962.1:c.4257G>T NP_001394891.1:p.Leu1419Phe missense NM_001407963.1:c.4254G>T NP_001394892.1:p.Leu1418Phe missense NM_001407965.1:c.4134G>T NP_001394894.1:p.Leu1378Phe missense NM_001407966.1:c.3753G>T NP_001394895.1:p.Leu1251Phe missense NM_001407967.1:c.3750G>T NP_001394896.1:p.Leu1250Phe missense NM_001407968.1:c.2037G>T NP_001394897.1:p.Leu679Phe missense NM_001407969.1:c.2034G>T NP_001394898.1:p.Leu678Phe missense NM_001407970.1:c.1398G>T NP_001394899.1:p.Leu466Phe missense NM_001407971.1:c.1398G>T NP_001394900.1:p.Leu466Phe missense NM_001407972.1:c.1395G>T NP_001394901.1:p.Leu465Phe missense NM_001407973.1:c.1332G>T NP_001394902.1:p.Leu444Phe missense NM_001407974.1:c.1332G>T NP_001394903.1:p.Leu444Phe missense NM_001407975.1:c.1332G>T NP_001394904.1:p.Leu444Phe missense NM_001407976.1:c.1332G>T NP_001394905.1:p.Leu444Phe missense NM_001407977.1:c.1332G>T NP_001394906.1:p.Leu444Phe missense NM_001407978.1:c.1332G>T NP_001394907.1:p.Leu444Phe missense NM_001407979.1:c.1329G>T NP_001394908.1:p.Leu443Phe missense NM_001407980.1:c.1329G>T NP_001394909.1:p.Leu443Phe missense NM_001407981.1:c.1329G>T NP_001394910.1:p.Leu443Phe missense NM_001407982.1:c.1329G>T NP_001394911.1:p.Leu443Phe missense NM_001407983.1:c.1329G>T NP_001394912.1:p.Leu443Phe missense NM_001407984.1:c.1329G>T NP_001394913.1:p.Leu443Phe missense NM_001407985.1:c.1329G>T NP_001394914.1:p.Leu443Phe missense NM_001407986.1:c.1329G>T NP_001394915.1:p.Leu443Phe missense NM_001407990.1:c.1329G>T NP_001394919.1:p.Leu443Phe missense NM_001407991.1:c.1329G>T NP_001394920.1:p.Leu443Phe missense NM_001407992.1:c.1329G>T NP_001394921.1:p.Leu443Phe missense NM_001407993.1:c.1329G>T NP_001394922.1:p.Leu443Phe missense NM_001408392.1:c.1326G>T NP_001395321.1:p.Leu442Phe missense NM_001408396.1:c.1326G>T NP_001395325.1:p.Leu442Phe missense NM_001408397.1:c.1326G>T NP_001395326.1:p.Leu442Phe missense NM_001408398.1:c.1326G>T NP_001395327.1:p.Leu442Phe missense NM_001408399.1:c.1326G>T NP_001395328.1:p.Leu442Phe missense NM_001408400.1:c.1326G>T NP_001395329.1:p.Leu442Phe missense NM_001408401.1:c.1326G>T NP_001395330.1:p.Leu442Phe missense NM_001408402.1:c.1326G>T NP_001395331.1:p.Leu442Phe missense NM_001408403.1:c.1326G>T NP_001395332.1:p.Leu442Phe missense NM_001408404.1:c.1326G>T NP_001395333.1:p.Leu442Phe missense NM_001408406.1:c.1323G>T NP_001395335.1:p.Leu441Phe missense NM_001408407.1:c.1323G>T NP_001395336.1:p.Leu441Phe missense NM_001408408.1:c.1323G>T NP_001395337.1:p.Leu441Phe missense NM_001408409.1:c.1320G>T NP_001395338.1:p.Leu440Phe missense NM_001408410.1:c.1257G>T NP_001395339.1:p.Leu419Phe missense NM_001408411.1:c.1254G>T NP_001395340.1:p.Leu418Phe missense NM_001408412.1:c.1251G>T NP_001395341.1:p.Leu417Phe missense NM_001408413.1:c.1251G>T NP_001395342.1:p.Leu417Phe missense NM_001408414.1:c.1251G>T NP_001395343.1:p.Leu417Phe missense NM_001408415.1:c.1251G>T NP_001395344.1:p.Leu417Phe missense NM_001408416.1:c.1251G>T NP_001395345.1:p.Leu417Phe missense NM_001408418.1:c.1215G>T NP_001395347.1:p.Leu405Phe missense NM_001408419.1:c.1215G>T NP_001395348.1:p.Leu405Phe missense NM_001408420.1:c.1215G>T NP_001395349.1:p.Leu405Phe missense NM_001408421.1:c.1212G>T NP_001395350.1:p.Leu404Phe missense NM_001408422.1:c.1212G>T NP_001395351.1:p.Leu404Phe missense NM_001408423.1:c.1212G>T NP_001395352.1:p.Leu404Phe missense NM_001408424.1:c.1212G>T NP_001395353.1:p.Leu404Phe missense NM_001408425.1:c.1209G>T NP_001395354.1:p.Leu403Phe missense NM_001408426.1:c.1209G>T NP_001395355.1:p.Leu403Phe missense NM_001408427.1:c.1209G>T NP_001395356.1:p.Leu403Phe missense NM_001408428.1:c.1209G>T NP_001395357.1:p.Leu403Phe missense NM_001408429.1:c.1209G>T NP_001395358.1:p.Leu403Phe missense NM_001408430.1:c.1209G>T NP_001395359.1:p.Leu403Phe missense NM_001408431.1:c.1209G>T NP_001395360.1:p.Leu403Phe missense NM_001408432.1:c.1206G>T NP_001395361.1:p.Leu402Phe missense NM_001408433.1:c.1206G>T NP_001395362.1:p.Leu402Phe missense NM_001408434.1:c.1206G>T NP_001395363.1:p.Leu402Phe missense NM_001408435.1:c.1206G>T NP_001395364.1:p.Leu402Phe missense NM_001408436.1:c.1206G>T NP_001395365.1:p.Leu402Phe missense NM_001408437.1:c.1206G>T NP_001395366.1:p.Leu402Phe missense NM_001408438.1:c.1206G>T NP_001395367.1:p.Leu402Phe missense NM_001408439.1:c.1206G>T NP_001395368.1:p.Leu402Phe missense NM_001408440.1:c.1206G>T NP_001395369.1:p.Leu402Phe missense NM_001408441.1:c.1206G>T NP_001395370.1:p.Leu402Phe missense NM_001408442.1:c.1206G>T NP_001395371.1:p.Leu402Phe missense NM_001408443.1:c.1206G>T NP_001395372.1:p.Leu402Phe missense NM_001408444.1:c.1206G>T NP_001395373.1:p.Leu402Phe missense NM_001408445.1:c.1203G>T NP_001395374.1:p.Leu401Phe missense NM_001408446.1:c.1203G>T NP_001395375.1:p.Leu401Phe missense NM_001408447.1:c.1203G>T NP_001395376.1:p.Leu401Phe missense NM_001408448.1:c.1203G>T NP_001395377.1:p.Leu401Phe missense NM_001408450.1:c.1203G>T NP_001395379.1:p.Leu401Phe missense NM_001408451.1:c.1197G>T NP_001395380.1:p.Leu399Phe missense NM_001408452.1:c.1191G>T NP_001395381.1:p.Leu397Phe missense NM_001408453.1:c.1191G>T NP_001395382.1:p.Leu397Phe missense NM_001408454.1:c.1191G>T NP_001395383.1:p.Leu397Phe missense NM_001408455.1:c.1191G>T NP_001395384.1:p.Leu397Phe missense NM_001408456.1:c.1191G>T NP_001395385.1:p.Leu397Phe missense NM_001408457.1:c.1191G>T NP_001395386.1:p.Leu397Phe missense NM_001408458.1:c.1188G>T NP_001395387.1:p.Leu396Phe missense NM_001408459.1:c.1188G>T NP_001395388.1:p.Leu396Phe missense NM_001408460.1:c.1188G>T NP_001395389.1:p.Leu396Phe missense NM_001408461.1:c.1188G>T NP_001395390.1:p.Leu396Phe missense NM_001408462.1:c.1188G>T NP_001395391.1:p.Leu396Phe missense NM_001408463.1:c.1188G>T NP_001395392.1:p.Leu396Phe missense NM_001408464.1:c.1188G>T NP_001395393.1:p.Leu396Phe missense NM_001408465.1:c.1188G>T NP_001395394.1:p.Leu396Phe missense NM_001408466.1:c.1188G>T NP_001395395.1:p.Leu396Phe missense NM_001408467.1:c.1188G>T NP_001395396.1:p.Leu396Phe missense NM_001408468.1:c.1185G>T NP_001395397.1:p.Leu395Phe missense NM_001408469.1:c.1185G>T NP_001395398.1:p.Leu395Phe missense NM_001408470.1:c.1185G>T NP_001395399.1:p.Leu395Phe missense NM_001408472.1:c.1329G>T NP_001395401.1:p.Leu443Phe missense NM_001408473.1:c.1326G>T NP_001395402.1:p.Leu442Phe missense NM_001408474.1:c.1131G>T NP_001395403.1:p.Leu377Phe missense NM_001408475.1:c.1128G>T NP_001395404.1:p.Leu376Phe missense NM_001408476.1:c.1128G>T NP_001395405.1:p.Leu376Phe missense NM_001408478.1:c.1122G>T NP_001395407.1:p.Leu374Phe missense NM_001408479.1:c.1122G>T NP_001395408.1:p.Leu374Phe missense NM_001408480.1:c.1122G>T NP_001395409.1:p.Leu374Phe missense NM_001408481.1:c.1119G>T NP_001395410.1:p.Leu373Phe missense NM_001408482.1:c.1119G>T NP_001395411.1:p.Leu373Phe missense NM_001408483.1:c.1119G>T NP_001395412.1:p.Leu373Phe missense NM_001408484.1:c.1119G>T NP_001395413.1:p.Leu373Phe missense NM_001408485.1:c.1119G>T NP_001395414.1:p.Leu373Phe missense NM_001408489.1:c.1119G>T NP_001395418.1:p.Leu373Phe missense NM_001408490.1:c.1119G>T NP_001395419.1:p.Leu373Phe missense NM_001408491.1:c.1119G>T NP_001395420.1:p.Leu373Phe missense NM_001408492.1:c.1116G>T NP_001395421.1:p.Leu372Phe missense NM_001408493.1:c.1116G>T NP_001395422.1:p.Leu372Phe missense NM_001408494.1:c.1092G>T NP_001395423.1:p.Leu364Phe missense NM_001408495.1:c.1086G>T NP_001395424.1:p.Leu362Phe missense NM_001408496.1:c.1068G>T NP_001395425.1:p.Leu356Phe missense NM_001408497.1:c.1068G>T NP_001395426.1:p.Leu356Phe missense NM_001408498.1:c.1068G>T NP_001395427.1:p.Leu356Phe missense NM_001408499.1:c.1068G>T NP_001395428.1:p.Leu356Phe missense NM_001408500.1:c.1068G>T NP_001395429.1:p.Leu356Phe missense NM_001408501.1:c.1068G>T NP_001395430.1:p.Leu356Phe missense NM_001408502.1:c.1065G>T NP_001395431.1:p.Leu355Phe missense NM_001408503.1:c.1065G>T NP_001395432.1:p.Leu355Phe missense NM_001408504.1:c.1065G>T NP_001395433.1:p.Leu355Phe missense NM_001408505.1:c.1062G>T NP_001395434.1:p.Leu354Phe missense NM_001408506.1:c.1005G>T NP_001395435.1:p.Leu335Phe missense NM_001408507.1:c.1002G>T NP_001395436.1:p.Leu334Phe missense NM_001408508.1:c.993G>T NP_001395437.1:p.Leu331Phe missense NM_001408509.1:c.990G>T NP_001395438.1:p.Leu330Phe missense NM_001408510.1:c.951G>T NP_001395439.1:p.Leu317Phe missense NM_001408511.1:c.948G>T NP_001395440.1:p.Leu316Phe missense NM_001408512.1:c.828G>T NP_001395441.1:p.Leu276Phe missense NM_007297.4:c.4500G>T NP_009228.2:p.Leu1500Phe missense NM_007298.4:c.1329G>T NP_009229.2:p.Leu443Phe missense NM_007299.4:c.1329G>T NP_009230.2:p.Leu443Phe missense NM_007300.4:c.4704G>T NP_009231.2:p.Leu1568Phe missense NM_007304.2:c.1329G>T NP_009235.2:p.Leu443Phe missense NR_027676.2:n.4818G>T non-coding transcript variant NC_000017.11:g.43074365C>A NC_000017.10:g.41226382C>A NG_005905.2:g.143619G>T LRG_292:g.143619G>T LRG_292t1:c.4641G>T LRG_292p1:p.Leu1547Phe - Protein change
- L1547F, L1568F, L443F, L1500F, L1420F, L1457F, L1477F, L1478F, L1506F, L1519F, L1521F, L1527F, L331F, L335F, L356F, L364F, L377F, L395F, L399F, L401F, L405F, L465F, L679F, L1476F, L1498F, L1505F, L1520F, L1528F, L1546F, L276F, L317F, L330F, L334F, L355F, L362F, L374F, L396F, L403F, L417F, L419F, L442F, L466F, L678F, L1251F, L1378F, L1434F, L1436F, L1458F, L1499F, L1503F, L1543F, L1544F, L1567F, L373F, L376F, L402F, L404F, L441F, L1250F, L1418F, L1419F, L1435F, L1459F, L1475F, L1480F, L1504F, L1542F, L1545F, L1569F, L316F, L354F, L372F, L397F, L418F, L440F, L444F
- Other names
- -
- Canonical SPDI
- NC_000017.11:43074364:C:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe 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
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Dec 7, 2016 | RCV000206692.8 |
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
(Dec 07, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000259902.5
First in ClinVar: Feb 02, 2016 Last updated: Feb 28, 2024 |
Comment:
In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, … (more)
In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The phenylalanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. This sequence change replaces leucine with phenylalanine at codon 1547 of the BRCA1 protein (p.Leu1547Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. (less)
|
Comment:
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:
In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The phenylalanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. This sequence change replaces leucine with phenylalanine at codon 1547 of the BRCA1 protein (p.Leu1547Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs864622265 ...
HelpThese 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 Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.