The p.S1580F variant (also known as c.4739C>T), located in coding exon 14 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4739. The serine at codon 1580 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This variant was detected in 1/2351 Italian breast and/or ovarian cancer patients (Santonocito C et al. Cancers (Basel), 2020 May;12). This variant had near wildtype activity in a transcriptional activation assay (Woods NT et al. NPJ Genom Med, 2016 Mar;1). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4739C>T (p.Ser1580Phe)
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.
(5)
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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
5
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.4739C>T (p.Ser1580Phe)
Variation ID: 55275 Accession: VCV000055275.17
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43071175 (GRCh38) [ NCBI UCSC ] 17: 41223192 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Apr 1, 2014 Jun 17, 2024 Dec 15, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4739C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ser1580Phe missense NM_001407571.1:c.4526C>T NP_001394500.1:p.Ser1509Phe missense NM_001407581.1:c.4805C>T NP_001394510.1:p.Ser1602Phe missense NM_001407582.1:c.4805C>T NP_001394511.1:p.Ser1602Phe missense NM_001407583.1:c.4802C>T NP_001394512.1:p.Ser1601Phe missense NM_001407585.1:c.4802C>T NP_001394514.1:p.Ser1601Phe missense NM_001407587.1:c.4802C>T NP_001394516.1:p.Ser1601Phe missense NM_001407590.1:c.4799C>T NP_001394519.1:p.Ser1600Phe missense NM_001407591.1:c.4799C>T NP_001394520.1:p.Ser1600Phe missense NM_001407593.1:c.4739C>T NP_001394522.1:p.Ser1580Phe missense NM_001407594.1:c.4739C>T NP_001394523.1:p.Ser1580Phe missense NM_001407596.1:c.4739C>T NP_001394525.1:p.Ser1580Phe missense NM_001407597.1:c.4739C>T NP_001394526.1:p.Ser1580Phe missense NM_001407598.1:c.4739C>T NP_001394527.1:p.Ser1580Phe missense NM_001407602.1:c.4739C>T NP_001394531.1:p.Ser1580Phe missense NM_001407603.1:c.4739C>T NP_001394532.1:p.Ser1580Phe missense NM_001407605.1:c.4739C>T NP_001394534.1:p.Ser1580Phe missense NM_001407610.1:c.4736C>T NP_001394539.1:p.Ser1579Phe missense NM_001407611.1:c.4736C>T NP_001394540.1:p.Ser1579Phe missense NM_001407612.1:c.4736C>T NP_001394541.1:p.Ser1579Phe missense NM_001407613.1:c.4736C>T NP_001394542.1:p.Ser1579Phe missense NM_001407614.1:c.4736C>T NP_001394543.1:p.Ser1579Phe missense NM_001407615.1:c.4736C>T NP_001394544.1:p.Ser1579Phe missense NM_001407616.1:c.4736C>T NP_001394545.1:p.Ser1579Phe missense NM_001407617.1:c.4736C>T NP_001394546.1:p.Ser1579Phe missense NM_001407618.1:c.4736C>T NP_001394547.1:p.Ser1579Phe missense NM_001407619.1:c.4736C>T NP_001394548.1:p.Ser1579Phe missense NM_001407620.1:c.4736C>T NP_001394549.1:p.Ser1579Phe missense NM_001407621.1:c.4736C>T NP_001394550.1:p.Ser1579Phe missense NM_001407622.1:c.4736C>T NP_001394551.1:p.Ser1579Phe missense NM_001407623.1:c.4736C>T NP_001394552.1:p.Ser1579Phe missense NM_001407624.1:c.4736C>T NP_001394553.1:p.Ser1579Phe missense NM_001407625.1:c.4736C>T NP_001394554.1:p.Ser1579Phe missense NM_001407626.1:c.4736C>T NP_001394555.1:p.Ser1579Phe missense NM_001407627.1:c.4733C>T NP_001394556.1:p.Ser1578Phe missense NM_001407628.1:c.4733C>T NP_001394557.1:p.Ser1578Phe missense NM_001407629.1:c.4733C>T NP_001394558.1:p.Ser1578Phe missense NM_001407630.1:c.4733C>T NP_001394559.1:p.Ser1578Phe missense NM_001407631.1:c.4733C>T NP_001394560.1:p.Ser1578Phe missense NM_001407632.1:c.4733C>T NP_001394561.1:p.Ser1578Phe missense NM_001407633.1:c.4733C>T NP_001394562.1:p.Ser1578Phe missense NM_001407634.1:c.4733C>T NP_001394563.1:p.Ser1578Phe missense NM_001407635.1:c.4733C>T NP_001394564.1:p.Ser1578Phe missense NM_001407636.1:c.4733C>T NP_001394565.1:p.Ser1578Phe missense NM_001407637.1:c.4733C>T NP_001394566.1:p.Ser1578Phe missense NM_001407638.1:c.4733C>T NP_001394567.1:p.Ser1578Phe missense NM_001407639.1:c.4733C>T NP_001394568.1:p.Ser1578Phe missense NM_001407640.1:c.4733C>T NP_001394569.1:p.Ser1578Phe missense NM_001407641.1:c.4733C>T NP_001394570.1:p.Ser1578Phe missense NM_001407642.1:c.4733C>T NP_001394571.1:p.Ser1578Phe missense NM_001407644.1:c.4730C>T NP_001394573.1:p.Ser1577Phe missense NM_001407645.1:c.4730C>T NP_001394574.1:p.Ser1577Phe missense NM_001407646.1:c.4727C>T NP_001394575.1:p.Ser1576Phe missense NM_001407647.1:c.4724C>T NP_001394576.1:p.Ser1575Phe missense NM_001407648.1:c.4682C>T NP_001394577.1:p.Ser1561Phe missense NM_001407649.1:c.4679C>T NP_001394578.1:p.Ser1560Phe missense NM_001407652.1:c.4739C>T NP_001394581.1:p.Ser1580Phe missense NM_001407653.1:c.4661C>T NP_001394582.1:p.Ser1554Phe missense NM_001407654.1:c.4661C>T NP_001394583.1:p.Ser1554Phe missense NM_001407655.1:c.4661C>T NP_001394584.1:p.Ser1554Phe missense NM_001407656.1:c.4658C>T NP_001394585.1:p.Ser1553Phe missense NM_001407657.1:c.4658C>T NP_001394586.1:p.Ser1553Phe missense NM_001407658.1:c.4658C>T NP_001394587.1:p.Ser1553Phe missense NM_001407659.1:c.4655C>T NP_001394588.1:p.Ser1552Phe missense NM_001407660.1:c.4655C>T NP_001394589.1:p.Ser1552Phe missense NM_001407661.1:c.4655C>T NP_001394590.1:p.Ser1552Phe missense NM_001407662.1:c.4655C>T NP_001394591.1:p.Ser1552Phe missense NM_001407663.1:c.4655C>T NP_001394592.1:p.Ser1552Phe missense NM_001407664.1:c.4616C>T NP_001394593.1:p.Ser1539Phe missense NM_001407665.1:c.4616C>T NP_001394594.1:p.Ser1539Phe missense NM_001407666.1:c.4616C>T NP_001394595.1:p.Ser1539Phe missense NM_001407667.1:c.4616C>T NP_001394596.1:p.Ser1539Phe missense NM_001407668.1:c.4616C>T NP_001394597.1:p.Ser1539Phe missense NM_001407669.1:c.4616C>T NP_001394598.1:p.Ser1539Phe missense NM_001407670.1:c.4613C>T NP_001394599.1:p.Ser1538Phe missense NM_001407671.1:c.4613C>T NP_001394600.1:p.Ser1538Phe missense NM_001407672.1:c.4613C>T NP_001394601.1:p.Ser1538Phe missense NM_001407673.1:c.4613C>T NP_001394602.1:p.Ser1538Phe missense NM_001407674.1:c.4613C>T NP_001394603.1:p.Ser1538Phe missense NM_001407675.1:c.4613C>T NP_001394604.1:p.Ser1538Phe missense NM_001407676.1:c.4613C>T NP_001394605.1:p.Ser1538Phe missense NM_001407677.1:c.4613C>T NP_001394606.1:p.Ser1538Phe missense NM_001407678.1:c.4613C>T NP_001394607.1:p.Ser1538Phe missense NM_001407679.1:c.4613C>T NP_001394608.1:p.Ser1538Phe missense NM_001407680.1:c.4613C>T NP_001394609.1:p.Ser1538Phe missense NM_001407681.1:c.4610C>T NP_001394610.1:p.Ser1537Phe missense NM_001407682.1:c.4610C>T NP_001394611.1:p.Ser1537Phe missense NM_001407683.1:c.4610C>T NP_001394612.1:p.Ser1537Phe missense NM_001407684.1:c.4739C>T NP_001394613.1:p.Ser1580Phe missense NM_001407685.1:c.4610C>T NP_001394614.1:p.Ser1537Phe missense NM_001407686.1:c.4610C>T NP_001394615.1:p.Ser1537Phe missense NM_001407687.1:c.4610C>T NP_001394616.1:p.Ser1537Phe missense NM_001407688.1:c.4610C>T NP_001394617.1:p.Ser1537Phe missense NM_001407689.1:c.4610C>T NP_001394618.1:p.Ser1537Phe missense NM_001407690.1:c.4607C>T NP_001394619.1:p.Ser1536Phe missense NM_001407691.1:c.4607C>T NP_001394620.1:p.Ser1536Phe missense NM_001407692.1:c.4598C>T NP_001394621.1:p.Ser1533Phe missense NM_001407694.1:c.4598C>T NP_001394623.1:p.Ser1533Phe missense NM_001407695.1:c.4598C>T NP_001394624.1:p.Ser1533Phe missense NM_001407696.1:c.4598C>T NP_001394625.1:p.Ser1533Phe missense NM_001407697.1:c.4598C>T NP_001394626.1:p.Ser1533Phe missense NM_001407698.1:c.4598C>T NP_001394627.1:p.Ser1533Phe missense NM_001407724.1:c.4598C>T NP_001394653.1:p.Ser1533Phe missense NM_001407725.1:c.4598C>T NP_001394654.1:p.Ser1533Phe missense NM_001407726.1:c.4598C>T NP_001394655.1:p.Ser1533Phe missense NM_001407727.1:c.4598C>T NP_001394656.1:p.Ser1533Phe missense NM_001407728.1:c.4598C>T NP_001394657.1:p.Ser1533Phe missense NM_001407729.1:c.4598C>T NP_001394658.1:p.Ser1533Phe missense NM_001407730.1:c.4598C>T NP_001394659.1:p.Ser1533Phe missense NM_001407731.1:c.4598C>T NP_001394660.1:p.Ser1533Phe missense NM_001407732.1:c.4595C>T NP_001394661.1:p.Ser1532Phe missense NM_001407733.1:c.4595C>T NP_001394662.1:p.Ser1532Phe missense NM_001407734.1:c.4595C>T NP_001394663.1:p.Ser1532Phe missense NM_001407735.1:c.4595C>T NP_001394664.1:p.Ser1532Phe missense NM_001407736.1:c.4595C>T NP_001394665.1:p.Ser1532Phe missense NM_001407737.1:c.4595C>T NP_001394666.1:p.Ser1532Phe missense NM_001407738.1:c.4595C>T NP_001394667.1:p.Ser1532Phe missense NM_001407739.1:c.4595C>T NP_001394668.1:p.Ser1532Phe missense NM_001407740.1:c.4595C>T NP_001394669.1:p.Ser1532Phe missense NM_001407741.1:c.4595C>T NP_001394670.1:p.Ser1532Phe missense NM_001407742.1:c.4595C>T NP_001394671.1:p.Ser1532Phe missense NM_001407743.1:c.4595C>T NP_001394672.1:p.Ser1532Phe missense NM_001407744.1:c.4595C>T NP_001394673.1:p.Ser1532Phe missense NM_001407745.1:c.4595C>T NP_001394674.1:p.Ser1532Phe missense NM_001407746.1:c.4595C>T NP_001394675.1:p.Ser1532Phe missense NM_001407747.1:c.4595C>T NP_001394676.1:p.Ser1532Phe missense NM_001407748.1:c.4595C>T NP_001394677.1:p.Ser1532Phe missense NM_001407749.1:c.4595C>T NP_001394678.1:p.Ser1532Phe missense NM_001407750.1:c.4595C>T NP_001394679.1:p.Ser1532Phe missense NM_001407751.1:c.4595C>T NP_001394680.1:p.Ser1532Phe missense NM_001407752.1:c.4595C>T NP_001394681.1:p.Ser1532Phe missense NM_001407838.1:c.4592C>T NP_001394767.1:p.Ser1531Phe missense NM_001407839.1:c.4592C>T NP_001394768.1:p.Ser1531Phe missense NM_001407841.1:c.4592C>T NP_001394770.1:p.Ser1531Phe missense NM_001407842.1:c.4592C>T NP_001394771.1:p.Ser1531Phe missense NM_001407843.1:c.4592C>T NP_001394772.1:p.Ser1531Phe missense NM_001407844.1:c.4592C>T NP_001394773.1:p.Ser1531Phe missense NM_001407845.1:c.4592C>T NP_001394774.1:p.Ser1531Phe missense NM_001407846.1:c.4592C>T NP_001394775.1:p.Ser1531Phe missense NM_001407847.1:c.4592C>T NP_001394776.1:p.Ser1531Phe missense NM_001407848.1:c.4592C>T NP_001394777.1:p.Ser1531Phe missense NM_001407849.1:c.4592C>T NP_001394778.1:p.Ser1531Phe missense NM_001407850.1:c.4592C>T NP_001394779.1:p.Ser1531Phe missense NM_001407851.1:c.4592C>T NP_001394780.1:p.Ser1531Phe missense NM_001407852.1:c.4592C>T NP_001394781.1:p.Ser1531Phe missense NM_001407853.1:c.4592C>T NP_001394782.1:p.Ser1531Phe missense NM_001407854.1:c.4739C>T NP_001394783.1:p.Ser1580Phe missense NM_001407858.1:c.4736C>T NP_001394787.1:p.Ser1579Phe missense NM_001407859.1:c.4736C>T NP_001394788.1:p.Ser1579Phe missense NM_001407860.1:c.4736C>T NP_001394789.1:p.Ser1579Phe missense NM_001407861.1:c.4733C>T NP_001394790.1:p.Ser1578Phe missense NM_001407862.1:c.4538C>T NP_001394791.1:p.Ser1513Phe missense NM_001407863.1:c.4613C>T NP_001394792.1:p.Ser1538Phe missense NM_001407874.1:c.4532C>T NP_001394803.1:p.Ser1511Phe missense NM_001407875.1:c.4532C>T NP_001394804.1:p.Ser1511Phe missense NM_001407879.1:c.4529C>T NP_001394808.1:p.Ser1510Phe missense NM_001407881.1:c.4529C>T NP_001394810.1:p.Ser1510Phe missense NM_001407882.1:c.4529C>T NP_001394811.1:p.Ser1510Phe missense NM_001407884.1:c.4529C>T NP_001394813.1:p.Ser1510Phe missense NM_001407885.1:c.4529C>T NP_001394814.1:p.Ser1510Phe missense NM_001407886.1:c.4529C>T NP_001394815.1:p.Ser1510Phe missense NM_001407887.1:c.4529C>T NP_001394816.1:p.Ser1510Phe missense NM_001407889.1:c.4529C>T NP_001394818.1:p.Ser1510Phe missense NM_001407894.1:c.4526C>T NP_001394823.1:p.Ser1509Phe missense NM_001407895.1:c.4526C>T NP_001394824.1:p.Ser1509Phe missense NM_001407896.1:c.4526C>T NP_001394825.1:p.Ser1509Phe missense NM_001407897.1:c.4526C>T NP_001394826.1:p.Ser1509Phe missense NM_001407898.1:c.4526C>T NP_001394827.1:p.Ser1509Phe missense NM_001407899.1:c.4526C>T NP_001394828.1:p.Ser1509Phe missense NM_001407900.1:c.4526C>T NP_001394829.1:p.Ser1509Phe missense NM_001407902.1:c.4526C>T NP_001394831.1:p.Ser1509Phe missense NM_001407904.1:c.4526C>T NP_001394833.1:p.Ser1509Phe missense NM_001407906.1:c.4526C>T NP_001394835.1:p.Ser1509Phe missense NM_001407907.1:c.4526C>T NP_001394836.1:p.Ser1509Phe missense NM_001407908.1:c.4526C>T NP_001394837.1:p.Ser1509Phe missense NM_001407909.1:c.4526C>T NP_001394838.1:p.Ser1509Phe missense NM_001407910.1:c.4526C>T NP_001394839.1:p.Ser1509Phe missense NM_001407915.1:c.4523C>T NP_001394844.1:p.Ser1508Phe missense NM_001407916.1:c.4523C>T NP_001394845.1:p.Ser1508Phe missense NM_001407917.1:c.4523C>T NP_001394846.1:p.Ser1508Phe missense NM_001407918.1:c.4523C>T NP_001394847.1:p.Ser1508Phe missense NM_001407919.1:c.4616C>T NP_001394848.1:p.Ser1539Phe missense NM_001407920.1:c.4475C>T NP_001394849.1:p.Ser1492Phe missense NM_001407921.1:c.4475C>T NP_001394850.1:p.Ser1492Phe missense NM_001407922.1:c.4475C>T NP_001394851.1:p.Ser1492Phe missense NM_001407923.1:c.4475C>T NP_001394852.1:p.Ser1492Phe missense NM_001407924.1:c.4475C>T NP_001394853.1:p.Ser1492Phe missense NM_001407925.1:c.4475C>T NP_001394854.1:p.Ser1492Phe missense NM_001407926.1:c.4475C>T NP_001394855.1:p.Ser1492Phe missense NM_001407927.1:c.4472C>T NP_001394856.1:p.Ser1491Phe missense NM_001407928.1:c.4472C>T NP_001394857.1:p.Ser1491Phe missense NM_001407929.1:c.4472C>T NP_001394858.1:p.Ser1491Phe missense NM_001407930.1:c.4472C>T NP_001394859.1:p.Ser1491Phe missense NM_001407931.1:c.4472C>T NP_001394860.1:p.Ser1491Phe missense NM_001407932.1:c.4472C>T NP_001394861.1:p.Ser1491Phe missense NM_001407933.1:c.4472C>T NP_001394862.1:p.Ser1491Phe missense NM_001407934.1:c.4469C>T NP_001394863.1:p.Ser1490Phe missense NM_001407935.1:c.4469C>T NP_001394864.1:p.Ser1490Phe missense NM_001407936.1:c.4469C>T NP_001394865.1:p.Ser1490Phe missense NM_001407937.1:c.4616C>T NP_001394866.1:p.Ser1539Phe missense NM_001407938.1:c.4616C>T NP_001394867.1:p.Ser1539Phe missense NM_001407939.1:c.4613C>T NP_001394868.1:p.Ser1538Phe missense NM_001407940.1:c.4613C>T NP_001394869.1:p.Ser1538Phe missense NM_001407941.1:c.4610C>T NP_001394870.1:p.Ser1537Phe missense NM_001407942.1:c.4598C>T NP_001394871.1:p.Ser1533Phe missense NM_001407943.1:c.4595C>T NP_001394872.1:p.Ser1532Phe missense NM_001407944.1:c.4595C>T NP_001394873.1:p.Ser1532Phe missense NM_001407945.1:c.4595C>T NP_001394874.1:p.Ser1532Phe missense NM_001407946.1:c.4406C>T NP_001394875.1:p.Ser1469Phe missense NM_001407947.1:c.4406C>T NP_001394876.1:p.Ser1469Phe missense NM_001407948.1:c.4406C>T NP_001394877.1:p.Ser1469Phe missense NM_001407949.1:c.4406C>T NP_001394878.1:p.Ser1469Phe missense NM_001407950.1:c.4403C>T NP_001394879.1:p.Ser1468Phe missense NM_001407951.1:c.4403C>T NP_001394880.1:p.Ser1468Phe missense NM_001407952.1:c.4403C>T NP_001394881.1:p.Ser1468Phe missense NM_001407953.1:c.4403C>T NP_001394882.1:p.Ser1468Phe missense NM_001407954.1:c.4403C>T NP_001394883.1:p.Ser1468Phe missense NM_001407955.1:c.4403C>T NP_001394884.1:p.Ser1468Phe missense NM_001407956.1:c.4400C>T NP_001394885.1:p.Ser1467Phe missense NM_001407957.1:c.4400C>T NP_001394886.1:p.Ser1467Phe missense NM_001407958.1:c.4400C>T NP_001394887.1:p.Ser1467Phe missense NM_001407959.1:c.4358C>T NP_001394888.1:p.Ser1453Phe missense NM_001407960.1:c.4355C>T NP_001394889.1:p.Ser1452Phe missense NM_001407962.1:c.4355C>T NP_001394891.1:p.Ser1452Phe missense NM_001407963.1:c.4352C>T NP_001394892.1:p.Ser1451Phe missense NM_001407964.1:c.4277C>T NP_001394893.1:p.Ser1426Phe missense NM_001407965.1:c.4232C>T NP_001394894.1:p.Ser1411Phe missense NM_001407966.1:c.3851C>T NP_001394895.1:p.Ser1284Phe missense NM_001407967.1:c.3848C>T NP_001394896.1:p.Ser1283Phe missense NM_001407968.1:c.2135C>T NP_001394897.1:p.Ser712Phe missense NM_001407969.1:c.2132C>T NP_001394898.1:p.Ser711Phe missense NM_001407970.1:c.1496C>T NP_001394899.1:p.Ser499Phe missense NM_001407971.1:c.1496C>T NP_001394900.1:p.Ser499Phe missense NM_001407972.1:c.1493C>T NP_001394901.1:p.Ser498Phe missense NM_001407973.1:c.1430C>T NP_001394902.1:p.Ser477Phe missense NM_001407974.1:c.1430C>T NP_001394903.1:p.Ser477Phe missense NM_001407975.1:c.1430C>T NP_001394904.1:p.Ser477Phe missense NM_001407976.1:c.1430C>T NP_001394905.1:p.Ser477Phe missense NM_001407977.1:c.1430C>T NP_001394906.1:p.Ser477Phe missense NM_001407978.1:c.1430C>T NP_001394907.1:p.Ser477Phe missense NM_001407979.1:c.1427C>T NP_001394908.1:p.Ser476Phe missense NM_001407980.1:c.1427C>T NP_001394909.1:p.Ser476Phe missense NM_001407981.1:c.1427C>T NP_001394910.1:p.Ser476Phe missense NM_001407982.1:c.1427C>T NP_001394911.1:p.Ser476Phe missense NM_001407983.1:c.1427C>T NP_001394912.1:p.Ser476Phe missense NM_001407984.1:c.1427C>T NP_001394913.1:p.Ser476Phe missense NM_001407985.1:c.1427C>T NP_001394914.1:p.Ser476Phe missense NM_001407986.1:c.1427C>T NP_001394915.1:p.Ser476Phe missense NM_001407990.1:c.1427C>T NP_001394919.1:p.Ser476Phe missense NM_001407991.1:c.1427C>T NP_001394920.1:p.Ser476Phe missense NM_001407992.1:c.1427C>T NP_001394921.1:p.Ser476Phe missense NM_001407993.1:c.1427C>T NP_001394922.1:p.Ser476Phe missense NM_001408392.1:c.1424C>T NP_001395321.1:p.Ser475Phe missense NM_001408396.1:c.1424C>T NP_001395325.1:p.Ser475Phe missense NM_001408397.1:c.1424C>T NP_001395326.1:p.Ser475Phe missense NM_001408398.1:c.1424C>T NP_001395327.1:p.Ser475Phe missense NM_001408399.1:c.1424C>T NP_001395328.1:p.Ser475Phe missense NM_001408400.1:c.1424C>T NP_001395329.1:p.Ser475Phe missense NM_001408401.1:c.1424C>T NP_001395330.1:p.Ser475Phe missense NM_001408402.1:c.1424C>T NP_001395331.1:p.Ser475Phe missense NM_001408403.1:c.1424C>T NP_001395332.1:p.Ser475Phe missense NM_001408404.1:c.1424C>T NP_001395333.1:p.Ser475Phe missense NM_001408406.1:c.1421C>T NP_001395335.1:p.Ser474Phe missense NM_001408407.1:c.1421C>T NP_001395336.1:p.Ser474Phe missense NM_001408408.1:c.1421C>T NP_001395337.1:p.Ser474Phe missense NM_001408409.1:c.1418C>T NP_001395338.1:p.Ser473Phe missense NM_001408410.1:c.1355C>T NP_001395339.1:p.Ser452Phe missense NM_001408411.1:c.1352C>T NP_001395340.1:p.Ser451Phe missense NM_001408412.1:c.1349C>T NP_001395341.1:p.Ser450Phe missense NM_001408413.1:c.1349C>T NP_001395342.1:p.Ser450Phe missense NM_001408414.1:c.1349C>T NP_001395343.1:p.Ser450Phe missense NM_001408415.1:c.1349C>T NP_001395344.1:p.Ser450Phe missense NM_001408416.1:c.1349C>T NP_001395345.1:p.Ser450Phe missense NM_001408418.1:c.1313C>T NP_001395347.1:p.Ser438Phe missense NM_001408419.1:c.1313C>T NP_001395348.1:p.Ser438Phe missense NM_001408420.1:c.1313C>T NP_001395349.1:p.Ser438Phe missense NM_001408421.1:c.1310C>T NP_001395350.1:p.Ser437Phe missense NM_001408422.1:c.1310C>T NP_001395351.1:p.Ser437Phe missense NM_001408423.1:c.1310C>T NP_001395352.1:p.Ser437Phe missense NM_001408424.1:c.1310C>T NP_001395353.1:p.Ser437Phe missense NM_001408425.1:c.1307C>T NP_001395354.1:p.Ser436Phe missense NM_001408426.1:c.1307C>T NP_001395355.1:p.Ser436Phe missense NM_001408427.1:c.1307C>T NP_001395356.1:p.Ser436Phe missense NM_001408428.1:c.1307C>T NP_001395357.1:p.Ser436Phe missense NM_001408429.1:c.1307C>T NP_001395358.1:p.Ser436Phe missense NM_001408430.1:c.1307C>T NP_001395359.1:p.Ser436Phe missense NM_001408431.1:c.1307C>T NP_001395360.1:p.Ser436Phe missense NM_001408432.1:c.1304C>T NP_001395361.1:p.Ser435Phe missense NM_001408433.1:c.1304C>T NP_001395362.1:p.Ser435Phe missense NM_001408434.1:c.1304C>T NP_001395363.1:p.Ser435Phe missense NM_001408435.1:c.1304C>T NP_001395364.1:p.Ser435Phe missense NM_001408436.1:c.1304C>T NP_001395365.1:p.Ser435Phe missense NM_001408437.1:c.1304C>T NP_001395366.1:p.Ser435Phe missense NM_001408438.1:c.1304C>T NP_001395367.1:p.Ser435Phe missense NM_001408439.1:c.1304C>T NP_001395368.1:p.Ser435Phe missense NM_001408440.1:c.1304C>T NP_001395369.1:p.Ser435Phe missense NM_001408441.1:c.1304C>T NP_001395370.1:p.Ser435Phe missense NM_001408442.1:c.1304C>T NP_001395371.1:p.Ser435Phe missense NM_001408443.1:c.1304C>T NP_001395372.1:p.Ser435Phe missense NM_001408444.1:c.1304C>T NP_001395373.1:p.Ser435Phe missense NM_001408445.1:c.1301C>T NP_001395374.1:p.Ser434Phe missense NM_001408446.1:c.1301C>T NP_001395375.1:p.Ser434Phe missense NM_001408447.1:c.1301C>T NP_001395376.1:p.Ser434Phe missense NM_001408448.1:c.1301C>T NP_001395377.1:p.Ser434Phe missense NM_001408450.1:c.1301C>T NP_001395379.1:p.Ser434Phe missense NM_001408451.1:c.1295C>T NP_001395380.1:p.Ser432Phe missense NM_001408452.1:c.1289C>T NP_001395381.1:p.Ser430Phe missense NM_001408453.1:c.1289C>T NP_001395382.1:p.Ser430Phe missense NM_001408454.1:c.1289C>T NP_001395383.1:p.Ser430Phe missense NM_001408455.1:c.1289C>T NP_001395384.1:p.Ser430Phe missense NM_001408456.1:c.1289C>T NP_001395385.1:p.Ser430Phe missense NM_001408457.1:c.1289C>T NP_001395386.1:p.Ser430Phe missense NM_001408458.1:c.1286C>T NP_001395387.1:p.Ser429Phe missense NM_001408459.1:c.1286C>T NP_001395388.1:p.Ser429Phe missense NM_001408460.1:c.1286C>T NP_001395389.1:p.Ser429Phe missense NM_001408461.1:c.1286C>T NP_001395390.1:p.Ser429Phe missense NM_001408462.1:c.1286C>T NP_001395391.1:p.Ser429Phe missense NM_001408463.1:c.1286C>T NP_001395392.1:p.Ser429Phe missense NM_001408464.1:c.1286C>T NP_001395393.1:p.Ser429Phe missense NM_001408465.1:c.1286C>T NP_001395394.1:p.Ser429Phe missense NM_001408466.1:c.1286C>T NP_001395395.1:p.Ser429Phe missense NM_001408467.1:c.1286C>T NP_001395396.1:p.Ser429Phe missense NM_001408468.1:c.1283C>T NP_001395397.1:p.Ser428Phe missense NM_001408469.1:c.1283C>T NP_001395398.1:p.Ser428Phe missense NM_001408470.1:c.1283C>T NP_001395399.1:p.Ser428Phe missense NM_001408472.1:c.1427C>T NP_001395401.1:p.Ser476Phe missense NM_001408473.1:c.1424C>T NP_001395402.1:p.Ser475Phe missense NM_001408474.1:c.1229C>T NP_001395403.1:p.Ser410Phe missense NM_001408475.1:c.1226C>T NP_001395404.1:p.Ser409Phe missense NM_001408476.1:c.1226C>T NP_001395405.1:p.Ser409Phe missense NM_001408478.1:c.1220C>T NP_001395407.1:p.Ser407Phe missense NM_001408479.1:c.1220C>T NP_001395408.1:p.Ser407Phe missense NM_001408480.1:c.1220C>T NP_001395409.1:p.Ser407Phe missense NM_001408481.1:c.1217C>T NP_001395410.1:p.Ser406Phe missense NM_001408482.1:c.1217C>T NP_001395411.1:p.Ser406Phe missense NM_001408483.1:c.1217C>T NP_001395412.1:p.Ser406Phe missense NM_001408484.1:c.1217C>T NP_001395413.1:p.Ser406Phe missense NM_001408485.1:c.1217C>T NP_001395414.1:p.Ser406Phe missense NM_001408489.1:c.1217C>T NP_001395418.1:p.Ser406Phe missense NM_001408490.1:c.1217C>T NP_001395419.1:p.Ser406Phe missense NM_001408491.1:c.1217C>T NP_001395420.1:p.Ser406Phe missense NM_001408492.1:c.1214C>T NP_001395421.1:p.Ser405Phe missense NM_001408493.1:c.1214C>T NP_001395422.1:p.Ser405Phe missense NM_001408494.1:c.1190C>T NP_001395423.1:p.Ser397Phe missense NM_001408495.1:c.1184C>T NP_001395424.1:p.Ser395Phe missense NM_001408496.1:c.1166C>T NP_001395425.1:p.Ser389Phe missense NM_001408497.1:c.1166C>T NP_001395426.1:p.Ser389Phe missense NM_001408498.1:c.1166C>T NP_001395427.1:p.Ser389Phe missense NM_001408499.1:c.1166C>T NP_001395428.1:p.Ser389Phe missense NM_001408500.1:c.1166C>T NP_001395429.1:p.Ser389Phe missense NM_001408501.1:c.1166C>T NP_001395430.1:p.Ser389Phe missense NM_001408502.1:c.1163C>T NP_001395431.1:p.Ser388Phe missense NM_001408503.1:c.1163C>T NP_001395432.1:p.Ser388Phe missense NM_001408504.1:c.1163C>T NP_001395433.1:p.Ser388Phe missense NM_001408505.1:c.1160C>T NP_001395434.1:p.Ser387Phe missense NM_001408506.1:c.1103C>T NP_001395435.1:p.Ser368Phe missense NM_001408507.1:c.1100C>T NP_001395436.1:p.Ser367Phe missense NM_001408508.1:c.1091C>T NP_001395437.1:p.Ser364Phe missense NM_001408509.1:c.1088C>T NP_001395438.1:p.Ser363Phe missense NM_001408510.1:c.1049C>T NP_001395439.1:p.Ser350Phe missense NM_001408511.1:c.1046C>T NP_001395440.1:p.Ser349Phe missense NM_001408512.1:c.926C>T NP_001395441.1:p.Ser309Phe missense NM_001408513.1:c.899C>T NP_001395442.1:p.Ser300Phe missense NM_007297.4:c.4598C>T NP_009228.2:p.Ser1533Phe missense NM_007298.4:c.1427C>T NP_009229.2:p.Ser476Phe missense NM_007299.4:c.1427C>T NP_009230.2:p.Ser476Phe missense NM_007300.4:c.4802C>T NP_009231.2:p.Ser1601Phe missense NM_007304.2:c.1427C>T NP_009235.2:p.Ser476Phe missense NR_027676.2:n.4916C>T non-coding transcript variant NC_000017.11:g.43071175G>A NC_000017.10:g.41223192G>A NG_005905.2:g.146809C>T LRG_292:g.146809C>T LRG_292t1:c.4739C>T LRG_292p1:p.Ser1580Phe U14680.1:n.4858C>T - Protein change
- S1580F, S1601F, S1533F, S476F, S1283F, S1411F, S1426F, S1452F, S1453F, S1469F, S1531F, S1536F, S1538F, S1553F, S1554F, S1575F, S1576F, S1579F, S300F, S367F, S389F, S429F, S435F, S450F, S451F, S473F, S475F, S499F, S711F, S1510F, S1532F, S1560F, S1577F, S309F, S364F, S368F, S387F, S395F, S409F, S410F, S430F, S434F, S438F, S474F, S498F, S712F, S1492F, S1467F, S1491F, S1509F, S1513F, S1539F, S1552F, S1561F, S1578F, S1600F, S349F, S350F, S388F, S405F, S407F, S432F, S437F, S477F, S1284F, S1451F, S1468F, S1490F, S1508F, S1511F, S1537F, S1602F, S363F, S397F, S406F, S428F, S436F, S452F
- Other names
- -
- Canonical SPDI
- NC_000017.11:43071174:G: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.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
- 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 (2) |
criteria provided, single submitter
|
Dec 15, 2023 | RCV000112392.4 | |
| Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Aug 14, 2023 | RCV000214535.8 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jul 29, 2022 | RCV001321689.6 |
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
(Aug 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000278602.6
First in ClinVar: May 29, 2016 Last updated: May 01, 2024 |
Comment:
The p.S1580F variant (also known as c.4739C>T), located in coding exon 14 of the BRCA1 gene, results from a C to T substitution at nucleotide … (more)
The p.S1580F variant (also known as c.4739C>T), located in coding exon 14 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4739. The serine at codon 1580 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This variant was detected in 1/2351 Italian breast and/or ovarian cancer patients (Santonocito C et al. Cancers (Basel), 2020 May;12). This variant had near wildtype activity in a transcriptional activation assay (Woods NT et al. NPJ Genom Med, 2016 Mar;1). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
|
|
Uncertain significance
(Dec 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV005058303.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
|
|
|
Uncertain significance
(Apr 12, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000909013.2
First in ClinVar: May 20, 2019 Last updated: Jun 22, 2020 |
|
|
|
Uncertain significance
(Jul 29, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001512530.4
First in ClinVar: Mar 14, 2021 Last updated: Feb 14, 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. ClinVar contains an entry for this variant (Variation ID: 55275). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 10923033). This variant is present in population databases (rs80357411, gnomAD 0.007%). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1580 of the BRCA1 protein (p.Ser1580Phe). (less)
|
|
|
Uncertain significance
(Nov 25, 2004)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145170.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 1
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Comment:
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. ClinVar contains an entry for this variant (Variation ID: 55275). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 10923033). This variant is present in population databases (rs80357411, gnomAD 0.007%). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1580 of the BRCA1 protein (p.Ser1580Phe).
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:
The p.S1580F variant (also known as c.4739C>T), located in coding exon 14 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4739. The serine at codon 1580 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This variant was detected in 1/2351 Italian breast and/or ovarian cancer patients (Santonocito C et al. Cancers (Basel), 2020 May;12). This variant had near wildtype activity in a transcriptional activation assay (Woods NT et al. NPJ Genom Med, 2016 Mar;1). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
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. ClinVar contains an entry for this variant (Variation ID: 55275). This missense change has been observed in individual(s) with clinical features of BRCA1-related conditions (PMID: 10923033). This variant is present in population databases (rs80357411, gnomAD 0.007%). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1580 of the BRCA1 protein (p.Ser1580Phe).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Spectrum of Germline BRCA1 and BRCA2 Variants Identified in 2351 Ovarian and Breast Cancer Patients Referring to a Reference Cancer Hospital of Rome. | Santonocito C | Cancers | 2020 | PMID: 32438681 |
| Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance. | Woods NT | NPJ genomic medicine | 2016 | PMID: 28781887 |
| The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
Text-mined citations for rs80357411 ...
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the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
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Record last updated Oct 08, 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.