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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 1575 of the BRCA1 protein (p.Pro1575Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4723C>A (p.Pro1575Thr)
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.4723C>A (p.Pro1575Thr)
Variation ID: 1488496 Accession: VCV001488496.7
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43071191 (GRCh38) [ NCBI UCSC ] 17: 41223208 (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 Mar 28, 2022 Feb 28, 2024 Jan 18, 2021 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4723C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Pro1575Thr missense NM_001407571.1:c.4510C>A NP_001394500.1:p.Pro1504Thr missense NM_001407581.1:c.4789C>A NP_001394510.1:p.Pro1597Thr missense NM_001407582.1:c.4789C>A NP_001394511.1:p.Pro1597Thr missense NM_001407583.1:c.4786C>A NP_001394512.1:p.Pro1596Thr missense NM_001407585.1:c.4786C>A NP_001394514.1:p.Pro1596Thr missense NM_001407587.1:c.4786C>A NP_001394516.1:p.Pro1596Thr missense NM_001407590.1:c.4783C>A NP_001394519.1:p.Pro1595Thr missense NM_001407591.1:c.4783C>A NP_001394520.1:p.Pro1595Thr missense NM_001407593.1:c.4723C>A NP_001394522.1:p.Pro1575Thr missense NM_001407594.1:c.4723C>A NP_001394523.1:p.Pro1575Thr missense NM_001407596.1:c.4723C>A NP_001394525.1:p.Pro1575Thr missense NM_001407597.1:c.4723C>A NP_001394526.1:p.Pro1575Thr missense NM_001407598.1:c.4723C>A NP_001394527.1:p.Pro1575Thr missense NM_001407602.1:c.4723C>A NP_001394531.1:p.Pro1575Thr missense NM_001407603.1:c.4723C>A NP_001394532.1:p.Pro1575Thr missense NM_001407605.1:c.4723C>A NP_001394534.1:p.Pro1575Thr missense NM_001407610.1:c.4720C>A NP_001394539.1:p.Pro1574Thr missense NM_001407611.1:c.4720C>A NP_001394540.1:p.Pro1574Thr missense NM_001407612.1:c.4720C>A NP_001394541.1:p.Pro1574Thr missense NM_001407613.1:c.4720C>A NP_001394542.1:p.Pro1574Thr missense NM_001407614.1:c.4720C>A NP_001394543.1:p.Pro1574Thr missense NM_001407615.1:c.4720C>A NP_001394544.1:p.Pro1574Thr missense NM_001407616.1:c.4720C>A NP_001394545.1:p.Pro1574Thr missense NM_001407617.1:c.4720C>A NP_001394546.1:p.Pro1574Thr missense NM_001407618.1:c.4720C>A NP_001394547.1:p.Pro1574Thr missense NM_001407619.1:c.4720C>A NP_001394548.1:p.Pro1574Thr missense NM_001407620.1:c.4720C>A NP_001394549.1:p.Pro1574Thr missense NM_001407621.1:c.4720C>A NP_001394550.1:p.Pro1574Thr missense NM_001407622.1:c.4720C>A NP_001394551.1:p.Pro1574Thr missense NM_001407623.1:c.4720C>A NP_001394552.1:p.Pro1574Thr missense NM_001407624.1:c.4720C>A NP_001394553.1:p.Pro1574Thr missense NM_001407625.1:c.4720C>A NP_001394554.1:p.Pro1574Thr missense NM_001407626.1:c.4720C>A NP_001394555.1:p.Pro1574Thr missense NM_001407627.1:c.4717C>A NP_001394556.1:p.Pro1573Thr missense NM_001407628.1:c.4717C>A NP_001394557.1:p.Pro1573Thr missense NM_001407629.1:c.4717C>A NP_001394558.1:p.Pro1573Thr missense NM_001407630.1:c.4717C>A NP_001394559.1:p.Pro1573Thr missense NM_001407631.1:c.4717C>A NP_001394560.1:p.Pro1573Thr missense NM_001407632.1:c.4717C>A NP_001394561.1:p.Pro1573Thr missense NM_001407633.1:c.4717C>A NP_001394562.1:p.Pro1573Thr missense NM_001407634.1:c.4717C>A NP_001394563.1:p.Pro1573Thr missense NM_001407635.1:c.4717C>A NP_001394564.1:p.Pro1573Thr missense NM_001407636.1:c.4717C>A NP_001394565.1:p.Pro1573Thr missense NM_001407637.1:c.4717C>A NP_001394566.1:p.Pro1573Thr missense NM_001407638.1:c.4717C>A NP_001394567.1:p.Pro1573Thr missense NM_001407639.1:c.4717C>A NP_001394568.1:p.Pro1573Thr missense NM_001407640.1:c.4717C>A NP_001394569.1:p.Pro1573Thr missense NM_001407641.1:c.4717C>A NP_001394570.1:p.Pro1573Thr missense NM_001407642.1:c.4717C>A NP_001394571.1:p.Pro1573Thr missense NM_001407644.1:c.4714C>A NP_001394573.1:p.Pro1572Thr missense NM_001407645.1:c.4714C>A NP_001394574.1:p.Pro1572Thr missense NM_001407646.1:c.4711C>A NP_001394575.1:p.Pro1571Thr missense NM_001407647.1:c.4708C>A NP_001394576.1:p.Pro1570Thr missense NM_001407648.1:c.4666C>A NP_001394577.1:p.Pro1556Thr missense NM_001407649.1:c.4663C>A NP_001394578.1:p.Pro1555Thr missense NM_001407652.1:c.4723C>A NP_001394581.1:p.Pro1575Thr missense NM_001407653.1:c.4645C>A NP_001394582.1:p.Pro1549Thr missense NM_001407654.1:c.4645C>A NP_001394583.1:p.Pro1549Thr missense NM_001407655.1:c.4645C>A NP_001394584.1:p.Pro1549Thr missense NM_001407656.1:c.4642C>A NP_001394585.1:p.Pro1548Thr missense NM_001407657.1:c.4642C>A NP_001394586.1:p.Pro1548Thr missense NM_001407658.1:c.4642C>A NP_001394587.1:p.Pro1548Thr missense NM_001407659.1:c.4639C>A NP_001394588.1:p.Pro1547Thr missense NM_001407660.1:c.4639C>A NP_001394589.1:p.Pro1547Thr missense NM_001407661.1:c.4639C>A NP_001394590.1:p.Pro1547Thr missense NM_001407662.1:c.4639C>A NP_001394591.1:p.Pro1547Thr missense NM_001407663.1:c.4639C>A NP_001394592.1:p.Pro1547Thr missense NM_001407664.1:c.4600C>A NP_001394593.1:p.Pro1534Thr missense NM_001407665.1:c.4600C>A NP_001394594.1:p.Pro1534Thr missense NM_001407666.1:c.4600C>A NP_001394595.1:p.Pro1534Thr missense NM_001407667.1:c.4600C>A NP_001394596.1:p.Pro1534Thr missense NM_001407668.1:c.4600C>A NP_001394597.1:p.Pro1534Thr missense NM_001407669.1:c.4600C>A NP_001394598.1:p.Pro1534Thr missense NM_001407670.1:c.4597C>A NP_001394599.1:p.Pro1533Thr missense NM_001407671.1:c.4597C>A NP_001394600.1:p.Pro1533Thr missense NM_001407672.1:c.4597C>A NP_001394601.1:p.Pro1533Thr missense NM_001407673.1:c.4597C>A NP_001394602.1:p.Pro1533Thr missense NM_001407674.1:c.4597C>A NP_001394603.1:p.Pro1533Thr missense NM_001407675.1:c.4597C>A NP_001394604.1:p.Pro1533Thr missense NM_001407676.1:c.4597C>A NP_001394605.1:p.Pro1533Thr missense NM_001407677.1:c.4597C>A NP_001394606.1:p.Pro1533Thr missense NM_001407678.1:c.4597C>A NP_001394607.1:p.Pro1533Thr missense NM_001407679.1:c.4597C>A NP_001394608.1:p.Pro1533Thr missense NM_001407680.1:c.4597C>A NP_001394609.1:p.Pro1533Thr missense NM_001407681.1:c.4594C>A NP_001394610.1:p.Pro1532Thr missense NM_001407682.1:c.4594C>A NP_001394611.1:p.Pro1532Thr missense NM_001407683.1:c.4594C>A NP_001394612.1:p.Pro1532Thr missense NM_001407684.1:c.4723C>A NP_001394613.1:p.Pro1575Thr missense NM_001407685.1:c.4594C>A NP_001394614.1:p.Pro1532Thr missense NM_001407686.1:c.4594C>A NP_001394615.1:p.Pro1532Thr missense NM_001407687.1:c.4594C>A NP_001394616.1:p.Pro1532Thr missense NM_001407688.1:c.4594C>A NP_001394617.1:p.Pro1532Thr missense NM_001407689.1:c.4594C>A NP_001394618.1:p.Pro1532Thr missense NM_001407690.1:c.4591C>A NP_001394619.1:p.Pro1531Thr missense NM_001407691.1:c.4591C>A NP_001394620.1:p.Pro1531Thr missense NM_001407692.1:c.4582C>A NP_001394621.1:p.Pro1528Thr missense NM_001407694.1:c.4582C>A NP_001394623.1:p.Pro1528Thr missense NM_001407695.1:c.4582C>A NP_001394624.1:p.Pro1528Thr missense NM_001407696.1:c.4582C>A NP_001394625.1:p.Pro1528Thr missense NM_001407697.1:c.4582C>A NP_001394626.1:p.Pro1528Thr missense NM_001407698.1:c.4582C>A NP_001394627.1:p.Pro1528Thr missense NM_001407724.1:c.4582C>A NP_001394653.1:p.Pro1528Thr missense NM_001407725.1:c.4582C>A NP_001394654.1:p.Pro1528Thr missense NM_001407726.1:c.4582C>A NP_001394655.1:p.Pro1528Thr missense NM_001407727.1:c.4582C>A NP_001394656.1:p.Pro1528Thr missense NM_001407728.1:c.4582C>A NP_001394657.1:p.Pro1528Thr missense NM_001407729.1:c.4582C>A NP_001394658.1:p.Pro1528Thr missense NM_001407730.1:c.4582C>A NP_001394659.1:p.Pro1528Thr missense NM_001407731.1:c.4582C>A NP_001394660.1:p.Pro1528Thr missense NM_001407732.1:c.4579C>A NP_001394661.1:p.Pro1527Thr missense NM_001407733.1:c.4579C>A NP_001394662.1:p.Pro1527Thr missense NM_001407734.1:c.4579C>A NP_001394663.1:p.Pro1527Thr missense NM_001407735.1:c.4579C>A NP_001394664.1:p.Pro1527Thr missense NM_001407736.1:c.4579C>A NP_001394665.1:p.Pro1527Thr missense NM_001407737.1:c.4579C>A NP_001394666.1:p.Pro1527Thr missense NM_001407738.1:c.4579C>A NP_001394667.1:p.Pro1527Thr missense NM_001407739.1:c.4579C>A NP_001394668.1:p.Pro1527Thr missense NM_001407740.1:c.4579C>A NP_001394669.1:p.Pro1527Thr missense NM_001407741.1:c.4579C>A NP_001394670.1:p.Pro1527Thr missense NM_001407742.1:c.4579C>A NP_001394671.1:p.Pro1527Thr missense NM_001407743.1:c.4579C>A NP_001394672.1:p.Pro1527Thr missense NM_001407744.1:c.4579C>A NP_001394673.1:p.Pro1527Thr missense NM_001407745.1:c.4579C>A NP_001394674.1:p.Pro1527Thr missense NM_001407746.1:c.4579C>A NP_001394675.1:p.Pro1527Thr missense NM_001407747.1:c.4579C>A NP_001394676.1:p.Pro1527Thr missense NM_001407748.1:c.4579C>A NP_001394677.1:p.Pro1527Thr missense NM_001407749.1:c.4579C>A NP_001394678.1:p.Pro1527Thr missense NM_001407750.1:c.4579C>A NP_001394679.1:p.Pro1527Thr missense NM_001407751.1:c.4579C>A NP_001394680.1:p.Pro1527Thr missense NM_001407752.1:c.4579C>A NP_001394681.1:p.Pro1527Thr missense NM_001407838.1:c.4576C>A NP_001394767.1:p.Pro1526Thr missense NM_001407839.1:c.4576C>A NP_001394768.1:p.Pro1526Thr missense NM_001407841.1:c.4576C>A NP_001394770.1:p.Pro1526Thr missense NM_001407842.1:c.4576C>A NP_001394771.1:p.Pro1526Thr missense NM_001407843.1:c.4576C>A NP_001394772.1:p.Pro1526Thr missense NM_001407844.1:c.4576C>A NP_001394773.1:p.Pro1526Thr missense NM_001407845.1:c.4576C>A NP_001394774.1:p.Pro1526Thr missense NM_001407846.1:c.4576C>A NP_001394775.1:p.Pro1526Thr missense NM_001407847.1:c.4576C>A NP_001394776.1:p.Pro1526Thr missense NM_001407848.1:c.4576C>A NP_001394777.1:p.Pro1526Thr missense NM_001407849.1:c.4576C>A NP_001394778.1:p.Pro1526Thr missense NM_001407850.1:c.4576C>A NP_001394779.1:p.Pro1526Thr missense NM_001407851.1:c.4576C>A NP_001394780.1:p.Pro1526Thr missense NM_001407852.1:c.4576C>A NP_001394781.1:p.Pro1526Thr missense NM_001407853.1:c.4576C>A NP_001394782.1:p.Pro1526Thr missense NM_001407854.1:c.4723C>A NP_001394783.1:p.Pro1575Thr missense NM_001407858.1:c.4720C>A NP_001394787.1:p.Pro1574Thr missense NM_001407859.1:c.4720C>A NP_001394788.1:p.Pro1574Thr missense NM_001407860.1:c.4720C>A NP_001394789.1:p.Pro1574Thr missense NM_001407861.1:c.4717C>A NP_001394790.1:p.Pro1573Thr missense NM_001407862.1:c.4522C>A NP_001394791.1:p.Pro1508Thr missense NM_001407863.1:c.4597C>A NP_001394792.1:p.Pro1533Thr missense NM_001407874.1:c.4516C>A NP_001394803.1:p.Pro1506Thr missense NM_001407875.1:c.4516C>A NP_001394804.1:p.Pro1506Thr missense NM_001407879.1:c.4513C>A NP_001394808.1:p.Pro1505Thr missense NM_001407881.1:c.4513C>A NP_001394810.1:p.Pro1505Thr missense NM_001407882.1:c.4513C>A NP_001394811.1:p.Pro1505Thr missense NM_001407884.1:c.4513C>A NP_001394813.1:p.Pro1505Thr missense NM_001407885.1:c.4513C>A NP_001394814.1:p.Pro1505Thr missense NM_001407886.1:c.4513C>A NP_001394815.1:p.Pro1505Thr missense NM_001407887.1:c.4513C>A NP_001394816.1:p.Pro1505Thr missense NM_001407889.1:c.4513C>A NP_001394818.1:p.Pro1505Thr missense NM_001407894.1:c.4510C>A NP_001394823.1:p.Pro1504Thr missense NM_001407895.1:c.4510C>A NP_001394824.1:p.Pro1504Thr missense NM_001407896.1:c.4510C>A NP_001394825.1:p.Pro1504Thr missense NM_001407897.1:c.4510C>A NP_001394826.1:p.Pro1504Thr missense NM_001407898.1:c.4510C>A NP_001394827.1:p.Pro1504Thr missense NM_001407899.1:c.4510C>A NP_001394828.1:p.Pro1504Thr missense NM_001407900.1:c.4510C>A NP_001394829.1:p.Pro1504Thr missense NM_001407902.1:c.4510C>A NP_001394831.1:p.Pro1504Thr missense NM_001407904.1:c.4510C>A NP_001394833.1:p.Pro1504Thr missense NM_001407906.1:c.4510C>A NP_001394835.1:p.Pro1504Thr missense NM_001407907.1:c.4510C>A NP_001394836.1:p.Pro1504Thr missense NM_001407908.1:c.4510C>A NP_001394837.1:p.Pro1504Thr missense NM_001407909.1:c.4510C>A NP_001394838.1:p.Pro1504Thr missense NM_001407910.1:c.4510C>A NP_001394839.1:p.Pro1504Thr missense NM_001407915.1:c.4507C>A NP_001394844.1:p.Pro1503Thr missense NM_001407916.1:c.4507C>A NP_001394845.1:p.Pro1503Thr missense NM_001407917.1:c.4507C>A NP_001394846.1:p.Pro1503Thr missense NM_001407918.1:c.4507C>A NP_001394847.1:p.Pro1503Thr missense NM_001407919.1:c.4600C>A NP_001394848.1:p.Pro1534Thr missense NM_001407920.1:c.4459C>A NP_001394849.1:p.Pro1487Thr missense NM_001407921.1:c.4459C>A NP_001394850.1:p.Pro1487Thr missense NM_001407922.1:c.4459C>A NP_001394851.1:p.Pro1487Thr missense NM_001407923.1:c.4459C>A NP_001394852.1:p.Pro1487Thr missense NM_001407924.1:c.4459C>A NP_001394853.1:p.Pro1487Thr missense NM_001407925.1:c.4459C>A NP_001394854.1:p.Pro1487Thr missense NM_001407926.1:c.4459C>A NP_001394855.1:p.Pro1487Thr missense NM_001407927.1:c.4456C>A NP_001394856.1:p.Pro1486Thr missense NM_001407928.1:c.4456C>A NP_001394857.1:p.Pro1486Thr missense NM_001407929.1:c.4456C>A NP_001394858.1:p.Pro1486Thr missense NM_001407930.1:c.4456C>A NP_001394859.1:p.Pro1486Thr missense NM_001407931.1:c.4456C>A NP_001394860.1:p.Pro1486Thr missense NM_001407932.1:c.4456C>A NP_001394861.1:p.Pro1486Thr missense NM_001407933.1:c.4456C>A NP_001394862.1:p.Pro1486Thr missense NM_001407934.1:c.4453C>A NP_001394863.1:p.Pro1485Thr missense NM_001407935.1:c.4453C>A NP_001394864.1:p.Pro1485Thr missense NM_001407936.1:c.4453C>A NP_001394865.1:p.Pro1485Thr missense NM_001407937.1:c.4600C>A NP_001394866.1:p.Pro1534Thr missense NM_001407938.1:c.4600C>A NP_001394867.1:p.Pro1534Thr missense NM_001407939.1:c.4597C>A NP_001394868.1:p.Pro1533Thr missense NM_001407940.1:c.4597C>A NP_001394869.1:p.Pro1533Thr missense NM_001407941.1:c.4594C>A NP_001394870.1:p.Pro1532Thr missense NM_001407942.1:c.4582C>A NP_001394871.1:p.Pro1528Thr missense NM_001407943.1:c.4579C>A NP_001394872.1:p.Pro1527Thr missense NM_001407944.1:c.4579C>A NP_001394873.1:p.Pro1527Thr missense NM_001407945.1:c.4579C>A NP_001394874.1:p.Pro1527Thr missense NM_001407946.1:c.4390C>A NP_001394875.1:p.Pro1464Thr missense NM_001407947.1:c.4390C>A NP_001394876.1:p.Pro1464Thr missense NM_001407948.1:c.4390C>A NP_001394877.1:p.Pro1464Thr missense NM_001407949.1:c.4390C>A NP_001394878.1:p.Pro1464Thr missense NM_001407950.1:c.4387C>A NP_001394879.1:p.Pro1463Thr missense NM_001407951.1:c.4387C>A NP_001394880.1:p.Pro1463Thr missense NM_001407952.1:c.4387C>A NP_001394881.1:p.Pro1463Thr missense NM_001407953.1:c.4387C>A NP_001394882.1:p.Pro1463Thr missense NM_001407954.1:c.4387C>A NP_001394883.1:p.Pro1463Thr missense NM_001407955.1:c.4387C>A NP_001394884.1:p.Pro1463Thr missense NM_001407956.1:c.4384C>A NP_001394885.1:p.Pro1462Thr missense NM_001407957.1:c.4384C>A NP_001394886.1:p.Pro1462Thr missense NM_001407958.1:c.4384C>A NP_001394887.1:p.Pro1462Thr missense NM_001407959.1:c.4342C>A NP_001394888.1:p.Pro1448Thr missense NM_001407960.1:c.4339C>A NP_001394889.1:p.Pro1447Thr missense NM_001407962.1:c.4339C>A NP_001394891.1:p.Pro1447Thr missense NM_001407963.1:c.4336C>A NP_001394892.1:p.Pro1446Thr missense NM_001407964.1:c.4261C>A NP_001394893.1:p.Pro1421Thr missense NM_001407965.1:c.4216C>A NP_001394894.1:p.Pro1406Thr missense NM_001407966.1:c.3835C>A NP_001394895.1:p.Pro1279Thr missense NM_001407967.1:c.3832C>A NP_001394896.1:p.Pro1278Thr missense NM_001407968.1:c.2119C>A NP_001394897.1:p.Pro707Thr missense NM_001407969.1:c.2116C>A NP_001394898.1:p.Pro706Thr missense NM_001407970.1:c.1480C>A NP_001394899.1:p.Pro494Thr missense NM_001407971.1:c.1480C>A NP_001394900.1:p.Pro494Thr missense NM_001407972.1:c.1477C>A NP_001394901.1:p.Pro493Thr missense NM_001407973.1:c.1414C>A NP_001394902.1:p.Pro472Thr missense NM_001407974.1:c.1414C>A NP_001394903.1:p.Pro472Thr missense NM_001407975.1:c.1414C>A NP_001394904.1:p.Pro472Thr missense NM_001407976.1:c.1414C>A NP_001394905.1:p.Pro472Thr missense NM_001407977.1:c.1414C>A NP_001394906.1:p.Pro472Thr missense NM_001407978.1:c.1414C>A NP_001394907.1:p.Pro472Thr missense NM_001407979.1:c.1411C>A NP_001394908.1:p.Pro471Thr missense NM_001407980.1:c.1411C>A NP_001394909.1:p.Pro471Thr missense NM_001407981.1:c.1411C>A NP_001394910.1:p.Pro471Thr missense NM_001407982.1:c.1411C>A NP_001394911.1:p.Pro471Thr missense NM_001407983.1:c.1411C>A NP_001394912.1:p.Pro471Thr missense NM_001407984.1:c.1411C>A NP_001394913.1:p.Pro471Thr missense NM_001407985.1:c.1411C>A NP_001394914.1:p.Pro471Thr missense NM_001407986.1:c.1411C>A NP_001394915.1:p.Pro471Thr missense NM_001407990.1:c.1411C>A NP_001394919.1:p.Pro471Thr missense NM_001407991.1:c.1411C>A NP_001394920.1:p.Pro471Thr missense NM_001407992.1:c.1411C>A NP_001394921.1:p.Pro471Thr missense NM_001407993.1:c.1411C>A NP_001394922.1:p.Pro471Thr missense NM_001408392.1:c.1408C>A NP_001395321.1:p.Pro470Thr missense NM_001408396.1:c.1408C>A NP_001395325.1:p.Pro470Thr missense NM_001408397.1:c.1408C>A NP_001395326.1:p.Pro470Thr missense NM_001408398.1:c.1408C>A NP_001395327.1:p.Pro470Thr missense NM_001408399.1:c.1408C>A NP_001395328.1:p.Pro470Thr missense NM_001408400.1:c.1408C>A NP_001395329.1:p.Pro470Thr missense NM_001408401.1:c.1408C>A NP_001395330.1:p.Pro470Thr missense NM_001408402.1:c.1408C>A NP_001395331.1:p.Pro470Thr missense NM_001408403.1:c.1408C>A NP_001395332.1:p.Pro470Thr missense NM_001408404.1:c.1408C>A NP_001395333.1:p.Pro470Thr missense NM_001408406.1:c.1405C>A NP_001395335.1:p.Pro469Thr missense NM_001408407.1:c.1405C>A NP_001395336.1:p.Pro469Thr missense NM_001408408.1:c.1405C>A NP_001395337.1:p.Pro469Thr missense NM_001408409.1:c.1402C>A NP_001395338.1:p.Pro468Thr missense NM_001408410.1:c.1339C>A NP_001395339.1:p.Pro447Thr missense NM_001408411.1:c.1336C>A NP_001395340.1:p.Pro446Thr missense NM_001408412.1:c.1333C>A NP_001395341.1:p.Pro445Thr missense NM_001408413.1:c.1333C>A NP_001395342.1:p.Pro445Thr missense NM_001408414.1:c.1333C>A NP_001395343.1:p.Pro445Thr missense NM_001408415.1:c.1333C>A NP_001395344.1:p.Pro445Thr missense NM_001408416.1:c.1333C>A NP_001395345.1:p.Pro445Thr missense NM_001408418.1:c.1297C>A NP_001395347.1:p.Pro433Thr missense NM_001408419.1:c.1297C>A NP_001395348.1:p.Pro433Thr missense NM_001408420.1:c.1297C>A NP_001395349.1:p.Pro433Thr missense NM_001408421.1:c.1294C>A NP_001395350.1:p.Pro432Thr missense NM_001408422.1:c.1294C>A NP_001395351.1:p.Pro432Thr missense NM_001408423.1:c.1294C>A NP_001395352.1:p.Pro432Thr missense NM_001408424.1:c.1294C>A NP_001395353.1:p.Pro432Thr missense NM_001408425.1:c.1291C>A NP_001395354.1:p.Pro431Thr missense NM_001408426.1:c.1291C>A NP_001395355.1:p.Pro431Thr missense NM_001408427.1:c.1291C>A NP_001395356.1:p.Pro431Thr missense NM_001408428.1:c.1291C>A NP_001395357.1:p.Pro431Thr missense NM_001408429.1:c.1291C>A NP_001395358.1:p.Pro431Thr missense NM_001408430.1:c.1291C>A NP_001395359.1:p.Pro431Thr missense NM_001408431.1:c.1291C>A NP_001395360.1:p.Pro431Thr missense NM_001408432.1:c.1288C>A NP_001395361.1:p.Pro430Thr missense NM_001408433.1:c.1288C>A NP_001395362.1:p.Pro430Thr missense NM_001408434.1:c.1288C>A NP_001395363.1:p.Pro430Thr missense NM_001408435.1:c.1288C>A NP_001395364.1:p.Pro430Thr missense NM_001408436.1:c.1288C>A NP_001395365.1:p.Pro430Thr missense NM_001408437.1:c.1288C>A NP_001395366.1:p.Pro430Thr missense NM_001408438.1:c.1288C>A NP_001395367.1:p.Pro430Thr missense NM_001408439.1:c.1288C>A NP_001395368.1:p.Pro430Thr missense NM_001408440.1:c.1288C>A NP_001395369.1:p.Pro430Thr missense NM_001408441.1:c.1288C>A NP_001395370.1:p.Pro430Thr missense NM_001408442.1:c.1288C>A NP_001395371.1:p.Pro430Thr missense NM_001408443.1:c.1288C>A NP_001395372.1:p.Pro430Thr missense NM_001408444.1:c.1288C>A NP_001395373.1:p.Pro430Thr missense NM_001408445.1:c.1285C>A NP_001395374.1:p.Pro429Thr missense NM_001408446.1:c.1285C>A NP_001395375.1:p.Pro429Thr missense NM_001408447.1:c.1285C>A NP_001395376.1:p.Pro429Thr missense NM_001408448.1:c.1285C>A NP_001395377.1:p.Pro429Thr missense NM_001408450.1:c.1285C>A NP_001395379.1:p.Pro429Thr missense NM_001408451.1:c.1279C>A NP_001395380.1:p.Pro427Thr missense NM_001408452.1:c.1273C>A NP_001395381.1:p.Pro425Thr missense NM_001408453.1:c.1273C>A NP_001395382.1:p.Pro425Thr missense NM_001408454.1:c.1273C>A NP_001395383.1:p.Pro425Thr missense NM_001408455.1:c.1273C>A NP_001395384.1:p.Pro425Thr missense NM_001408456.1:c.1273C>A NP_001395385.1:p.Pro425Thr missense NM_001408457.1:c.1273C>A NP_001395386.1:p.Pro425Thr missense NM_001408458.1:c.1270C>A NP_001395387.1:p.Pro424Thr missense NM_001408459.1:c.1270C>A NP_001395388.1:p.Pro424Thr missense NM_001408460.1:c.1270C>A NP_001395389.1:p.Pro424Thr missense NM_001408461.1:c.1270C>A NP_001395390.1:p.Pro424Thr missense NM_001408462.1:c.1270C>A NP_001395391.1:p.Pro424Thr missense NM_001408463.1:c.1270C>A NP_001395392.1:p.Pro424Thr missense NM_001408464.1:c.1270C>A NP_001395393.1:p.Pro424Thr missense NM_001408465.1:c.1270C>A NP_001395394.1:p.Pro424Thr missense NM_001408466.1:c.1270C>A NP_001395395.1:p.Pro424Thr missense NM_001408467.1:c.1270C>A NP_001395396.1:p.Pro424Thr missense NM_001408468.1:c.1267C>A NP_001395397.1:p.Pro423Thr missense NM_001408469.1:c.1267C>A NP_001395398.1:p.Pro423Thr missense NM_001408470.1:c.1267C>A NP_001395399.1:p.Pro423Thr missense NM_001408472.1:c.1411C>A NP_001395401.1:p.Pro471Thr missense NM_001408473.1:c.1408C>A NP_001395402.1:p.Pro470Thr missense NM_001408474.1:c.1213C>A NP_001395403.1:p.Pro405Thr missense NM_001408475.1:c.1210C>A NP_001395404.1:p.Pro404Thr missense NM_001408476.1:c.1210C>A NP_001395405.1:p.Pro404Thr missense NM_001408478.1:c.1204C>A NP_001395407.1:p.Pro402Thr missense NM_001408479.1:c.1204C>A NP_001395408.1:p.Pro402Thr missense NM_001408480.1:c.1204C>A NP_001395409.1:p.Pro402Thr missense NM_001408481.1:c.1201C>A NP_001395410.1:p.Pro401Thr missense NM_001408482.1:c.1201C>A NP_001395411.1:p.Pro401Thr missense NM_001408483.1:c.1201C>A NP_001395412.1:p.Pro401Thr missense NM_001408484.1:c.1201C>A NP_001395413.1:p.Pro401Thr missense NM_001408485.1:c.1201C>A NP_001395414.1:p.Pro401Thr missense NM_001408489.1:c.1201C>A NP_001395418.1:p.Pro401Thr missense NM_001408490.1:c.1201C>A NP_001395419.1:p.Pro401Thr missense NM_001408491.1:c.1201C>A NP_001395420.1:p.Pro401Thr missense NM_001408492.1:c.1198C>A NP_001395421.1:p.Pro400Thr missense NM_001408493.1:c.1198C>A NP_001395422.1:p.Pro400Thr missense NM_001408494.1:c.1174C>A NP_001395423.1:p.Pro392Thr missense NM_001408495.1:c.1168C>A NP_001395424.1:p.Pro390Thr missense NM_001408496.1:c.1150C>A NP_001395425.1:p.Pro384Thr missense NM_001408497.1:c.1150C>A NP_001395426.1:p.Pro384Thr missense NM_001408498.1:c.1150C>A NP_001395427.1:p.Pro384Thr missense NM_001408499.1:c.1150C>A NP_001395428.1:p.Pro384Thr missense NM_001408500.1:c.1150C>A NP_001395429.1:p.Pro384Thr missense NM_001408501.1:c.1150C>A NP_001395430.1:p.Pro384Thr missense NM_001408502.1:c.1147C>A NP_001395431.1:p.Pro383Thr missense NM_001408503.1:c.1147C>A NP_001395432.1:p.Pro383Thr missense NM_001408504.1:c.1147C>A NP_001395433.1:p.Pro383Thr missense NM_001408505.1:c.1144C>A NP_001395434.1:p.Pro382Thr missense NM_001408506.1:c.1087C>A NP_001395435.1:p.Pro363Thr missense NM_001408507.1:c.1084C>A NP_001395436.1:p.Pro362Thr missense NM_001408508.1:c.1075C>A NP_001395437.1:p.Pro359Thr missense NM_001408509.1:c.1072C>A NP_001395438.1:p.Pro358Thr missense NM_001408510.1:c.1033C>A NP_001395439.1:p.Pro345Thr missense NM_001408511.1:c.1030C>A NP_001395440.1:p.Pro344Thr missense NM_001408512.1:c.910C>A NP_001395441.1:p.Pro304Thr missense NM_001408513.1:c.883C>A NP_001395442.1:p.Pro295Thr missense NM_007297.4:c.4582C>A NP_009228.2:p.Pro1528Thr missense NM_007298.4:c.1411C>A NP_009229.2:p.Pro471Thr missense NM_007299.4:c.1411C>A NP_009230.2:p.Pro471Thr missense NM_007300.4:c.4786C>A NP_009231.2:p.Pro1596Thr missense NM_007304.2:c.1411C>A NP_009235.2:p.Pro471Thr missense NR_027676.2:n.4900C>A non-coding transcript variant NC_000017.11:g.43071191G>T NC_000017.10:g.41223208G>T NG_005905.2:g.146793C>A LRG_292:g.146793C>A LRG_292t1:c.4723C>A LRG_292p1:p.Pro1575Thr - Protein change
- P1528T, P1575T, P1596T, P471T, P1447T, P1462T, P1463T, P1486T, P1503T, P1531T, P1533T, P1548T, P1556T, P1570T, P1572T, P1574T, P1595T, P1597T, P295T, P358T, P363T, P382T, P384T, P427T, P431T, P432T, P446T, P469T, P706T, P1278T, P1279T, P1448T, P1487T, P1504T, P1505T, P1508T, P1527T, P1549T, P1573T, P359T, P383T, P390T, P400T, P424T, P429T, P433T, P447T, P470T, P472T, P494T, P707T, P1446T, P1464T, P1506T, P1534T, P1547T, P1555T, P1571T, P304T, P405T, P423T, P430T, P1406T, P1421T, P1485T, P1526T, P1532T, P344T, P345T, P362T, P392T, P401T, P402T, P404T, P425T, P445T, P468T, P493T
- Other names
- -
- Canonical SPDI
- NC_000017.11:43071190:G:T
-
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 |
13041 | 14847 | |
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
|
Jan 18, 2021 | RCV001988612.7 |
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
(Jan 18, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002273909.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
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 … (more)
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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 1575 of the BRCA1 protein (p.Pro1575Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. (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, 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 1575 of the BRCA1 protein (p.Pro1575Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine.
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 rs755370895 ...
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.