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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA1-related disease. This variant is present in population databases (rs137894496, ExAC 0.009%). This sequence change replaces leucine with phenylalanine at codon 1517 of the BRCA1 protein (p.Leu1517Phe). 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.4549C>T (p.Leu1517Phe)
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.
(2)
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
2
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.4549C>T (p.Leu1517Phe)
Variation ID: 661280 Accession: VCV000661280.10
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43074457 (GRCh38) [ NCBI UCSC ] 17: 41226474 (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 Aug 14, 2019 May 1, 2024 Mar 22, 2022 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4549C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Leu1517Phe missense NM_001407571.1:c.4336C>T NP_001394500.1:p.Leu1446Phe missense NM_001407581.1:c.4615C>T NP_001394510.1:p.Leu1539Phe missense NM_001407582.1:c.4615C>T NP_001394511.1:p.Leu1539Phe missense NM_001407583.1:c.4612C>T NP_001394512.1:p.Leu1538Phe missense NM_001407585.1:c.4612C>T NP_001394514.1:p.Leu1538Phe missense NM_001407587.1:c.4612C>T NP_001394516.1:p.Leu1538Phe missense NM_001407590.1:c.4609C>T NP_001394519.1:p.Leu1537Phe missense NM_001407591.1:c.4609C>T NP_001394520.1:p.Leu1537Phe missense NM_001407593.1:c.4549C>T NP_001394522.1:p.Leu1517Phe missense NM_001407594.1:c.4549C>T NP_001394523.1:p.Leu1517Phe missense NM_001407596.1:c.4549C>T NP_001394525.1:p.Leu1517Phe missense NM_001407597.1:c.4549C>T NP_001394526.1:p.Leu1517Phe missense NM_001407598.1:c.4549C>T NP_001394527.1:p.Leu1517Phe missense NM_001407602.1:c.4549C>T NP_001394531.1:p.Leu1517Phe missense NM_001407603.1:c.4549C>T NP_001394532.1:p.Leu1517Phe missense NM_001407605.1:c.4549C>T NP_001394534.1:p.Leu1517Phe missense NM_001407610.1:c.4546C>T NP_001394539.1:p.Leu1516Phe missense NM_001407611.1:c.4546C>T NP_001394540.1:p.Leu1516Phe missense NM_001407612.1:c.4546C>T NP_001394541.1:p.Leu1516Phe missense NM_001407613.1:c.4546C>T NP_001394542.1:p.Leu1516Phe missense NM_001407614.1:c.4546C>T NP_001394543.1:p.Leu1516Phe missense NM_001407615.1:c.4546C>T NP_001394544.1:p.Leu1516Phe missense NM_001407616.1:c.4546C>T NP_001394545.1:p.Leu1516Phe missense NM_001407617.1:c.4546C>T NP_001394546.1:p.Leu1516Phe missense NM_001407618.1:c.4546C>T NP_001394547.1:p.Leu1516Phe missense NM_001407619.1:c.4546C>T NP_001394548.1:p.Leu1516Phe missense NM_001407620.1:c.4546C>T NP_001394549.1:p.Leu1516Phe missense NM_001407621.1:c.4546C>T NP_001394550.1:p.Leu1516Phe missense NM_001407622.1:c.4546C>T NP_001394551.1:p.Leu1516Phe missense NM_001407623.1:c.4546C>T NP_001394552.1:p.Leu1516Phe missense NM_001407624.1:c.4546C>T NP_001394553.1:p.Leu1516Phe missense NM_001407625.1:c.4546C>T NP_001394554.1:p.Leu1516Phe missense NM_001407626.1:c.4546C>T NP_001394555.1:p.Leu1516Phe missense NM_001407627.1:c.4543C>T NP_001394556.1:p.Leu1515Phe missense NM_001407628.1:c.4543C>T NP_001394557.1:p.Leu1515Phe missense NM_001407629.1:c.4543C>T NP_001394558.1:p.Leu1515Phe missense NM_001407630.1:c.4543C>T NP_001394559.1:p.Leu1515Phe missense NM_001407631.1:c.4543C>T NP_001394560.1:p.Leu1515Phe missense NM_001407632.1:c.4543C>T NP_001394561.1:p.Leu1515Phe missense NM_001407633.1:c.4543C>T NP_001394562.1:p.Leu1515Phe missense NM_001407634.1:c.4543C>T NP_001394563.1:p.Leu1515Phe missense NM_001407635.1:c.4543C>T NP_001394564.1:p.Leu1515Phe missense NM_001407636.1:c.4543C>T NP_001394565.1:p.Leu1515Phe missense NM_001407637.1:c.4543C>T NP_001394566.1:p.Leu1515Phe missense NM_001407638.1:c.4543C>T NP_001394567.1:p.Leu1515Phe missense NM_001407639.1:c.4543C>T NP_001394568.1:p.Leu1515Phe missense NM_001407640.1:c.4543C>T NP_001394569.1:p.Leu1515Phe missense NM_001407641.1:c.4543C>T NP_001394570.1:p.Leu1515Phe missense NM_001407642.1:c.4543C>T NP_001394571.1:p.Leu1515Phe missense NM_001407644.1:c.4540C>T NP_001394573.1:p.Leu1514Phe missense NM_001407645.1:c.4540C>T NP_001394574.1:p.Leu1514Phe missense NM_001407646.1:c.4537C>T NP_001394575.1:p.Leu1513Phe missense NM_001407647.1:c.4534C>T NP_001394576.1:p.Leu1512Phe missense NM_001407648.1:c.4492C>T NP_001394577.1:p.Leu1498Phe missense NM_001407649.1:c.4489C>T NP_001394578.1:p.Leu1497Phe missense NM_001407652.1:c.4549C>T NP_001394581.1:p.Leu1517Phe missense NM_001407653.1:c.4471C>T NP_001394582.1:p.Leu1491Phe missense NM_001407654.1:c.4471C>T NP_001394583.1:p.Leu1491Phe missense NM_001407655.1:c.4471C>T NP_001394584.1:p.Leu1491Phe missense NM_001407656.1:c.4468C>T NP_001394585.1:p.Leu1490Phe missense NM_001407657.1:c.4468C>T NP_001394586.1:p.Leu1490Phe missense NM_001407658.1:c.4468C>T NP_001394587.1:p.Leu1490Phe missense NM_001407659.1:c.4465C>T NP_001394588.1:p.Leu1489Phe missense NM_001407660.1:c.4465C>T NP_001394589.1:p.Leu1489Phe missense NM_001407661.1:c.4465C>T NP_001394590.1:p.Leu1489Phe missense NM_001407662.1:c.4465C>T NP_001394591.1:p.Leu1489Phe missense NM_001407663.1:c.4465C>T NP_001394592.1:p.Leu1489Phe missense NM_001407664.1:c.4426C>T NP_001394593.1:p.Leu1476Phe missense NM_001407665.1:c.4426C>T NP_001394594.1:p.Leu1476Phe missense NM_001407666.1:c.4426C>T NP_001394595.1:p.Leu1476Phe missense NM_001407667.1:c.4426C>T NP_001394596.1:p.Leu1476Phe missense NM_001407668.1:c.4426C>T NP_001394597.1:p.Leu1476Phe missense NM_001407669.1:c.4426C>T NP_001394598.1:p.Leu1476Phe missense NM_001407670.1:c.4423C>T NP_001394599.1:p.Leu1475Phe missense NM_001407671.1:c.4423C>T NP_001394600.1:p.Leu1475Phe missense NM_001407672.1:c.4423C>T NP_001394601.1:p.Leu1475Phe missense NM_001407673.1:c.4423C>T NP_001394602.1:p.Leu1475Phe missense NM_001407674.1:c.4423C>T NP_001394603.1:p.Leu1475Phe missense NM_001407675.1:c.4423C>T NP_001394604.1:p.Leu1475Phe missense NM_001407676.1:c.4423C>T NP_001394605.1:p.Leu1475Phe missense NM_001407677.1:c.4423C>T NP_001394606.1:p.Leu1475Phe missense NM_001407678.1:c.4423C>T NP_001394607.1:p.Leu1475Phe missense NM_001407679.1:c.4423C>T NP_001394608.1:p.Leu1475Phe missense NM_001407680.1:c.4423C>T NP_001394609.1:p.Leu1475Phe missense NM_001407681.1:c.4420C>T NP_001394610.1:p.Leu1474Phe missense NM_001407682.1:c.4420C>T NP_001394611.1:p.Leu1474Phe missense NM_001407683.1:c.4420C>T NP_001394612.1:p.Leu1474Phe missense NM_001407684.1:c.4549C>T NP_001394613.1:p.Leu1517Phe missense NM_001407685.1:c.4420C>T NP_001394614.1:p.Leu1474Phe missense NM_001407686.1:c.4420C>T NP_001394615.1:p.Leu1474Phe missense NM_001407687.1:c.4420C>T NP_001394616.1:p.Leu1474Phe missense NM_001407688.1:c.4420C>T NP_001394617.1:p.Leu1474Phe missense NM_001407689.1:c.4420C>T NP_001394618.1:p.Leu1474Phe missense NM_001407690.1:c.4417C>T NP_001394619.1:p.Leu1473Phe missense NM_001407691.1:c.4417C>T NP_001394620.1:p.Leu1473Phe missense NM_001407692.1:c.4408C>T NP_001394621.1:p.Leu1470Phe missense NM_001407694.1:c.4408C>T NP_001394623.1:p.Leu1470Phe missense NM_001407695.1:c.4408C>T NP_001394624.1:p.Leu1470Phe missense NM_001407696.1:c.4408C>T NP_001394625.1:p.Leu1470Phe missense NM_001407697.1:c.4408C>T NP_001394626.1:p.Leu1470Phe missense NM_001407698.1:c.4408C>T NP_001394627.1:p.Leu1470Phe missense NM_001407724.1:c.4408C>T NP_001394653.1:p.Leu1470Phe missense NM_001407725.1:c.4408C>T NP_001394654.1:p.Leu1470Phe missense NM_001407726.1:c.4408C>T NP_001394655.1:p.Leu1470Phe missense NM_001407727.1:c.4408C>T NP_001394656.1:p.Leu1470Phe missense NM_001407728.1:c.4408C>T NP_001394657.1:p.Leu1470Phe missense NM_001407729.1:c.4408C>T NP_001394658.1:p.Leu1470Phe missense NM_001407730.1:c.4408C>T NP_001394659.1:p.Leu1470Phe missense NM_001407731.1:c.4408C>T NP_001394660.1:p.Leu1470Phe missense NM_001407732.1:c.4405C>T NP_001394661.1:p.Leu1469Phe missense NM_001407733.1:c.4405C>T NP_001394662.1:p.Leu1469Phe missense NM_001407734.1:c.4405C>T NP_001394663.1:p.Leu1469Phe missense NM_001407735.1:c.4405C>T NP_001394664.1:p.Leu1469Phe missense NM_001407736.1:c.4405C>T NP_001394665.1:p.Leu1469Phe missense NM_001407737.1:c.4405C>T NP_001394666.1:p.Leu1469Phe missense NM_001407738.1:c.4405C>T NP_001394667.1:p.Leu1469Phe missense NM_001407739.1:c.4405C>T NP_001394668.1:p.Leu1469Phe missense NM_001407740.1:c.4405C>T NP_001394669.1:p.Leu1469Phe missense NM_001407741.1:c.4405C>T NP_001394670.1:p.Leu1469Phe missense NM_001407742.1:c.4405C>T NP_001394671.1:p.Leu1469Phe missense NM_001407743.1:c.4405C>T NP_001394672.1:p.Leu1469Phe missense NM_001407744.1:c.4405C>T NP_001394673.1:p.Leu1469Phe missense NM_001407745.1:c.4405C>T NP_001394674.1:p.Leu1469Phe missense NM_001407746.1:c.4405C>T NP_001394675.1:p.Leu1469Phe missense NM_001407747.1:c.4405C>T NP_001394676.1:p.Leu1469Phe missense NM_001407748.1:c.4405C>T NP_001394677.1:p.Leu1469Phe missense NM_001407749.1:c.4405C>T NP_001394678.1:p.Leu1469Phe missense NM_001407750.1:c.4405C>T NP_001394679.1:p.Leu1469Phe missense NM_001407751.1:c.4405C>T NP_001394680.1:p.Leu1469Phe missense NM_001407752.1:c.4405C>T NP_001394681.1:p.Leu1469Phe missense NM_001407838.1:c.4402C>T NP_001394767.1:p.Leu1468Phe missense NM_001407839.1:c.4402C>T NP_001394768.1:p.Leu1468Phe missense NM_001407841.1:c.4402C>T NP_001394770.1:p.Leu1468Phe missense NM_001407842.1:c.4402C>T NP_001394771.1:p.Leu1468Phe missense NM_001407843.1:c.4402C>T NP_001394772.1:p.Leu1468Phe missense NM_001407844.1:c.4402C>T NP_001394773.1:p.Leu1468Phe missense NM_001407845.1:c.4402C>T NP_001394774.1:p.Leu1468Phe missense NM_001407846.1:c.4402C>T NP_001394775.1:p.Leu1468Phe missense NM_001407847.1:c.4402C>T NP_001394776.1:p.Leu1468Phe missense NM_001407848.1:c.4402C>T NP_001394777.1:p.Leu1468Phe missense NM_001407849.1:c.4402C>T NP_001394778.1:p.Leu1468Phe missense NM_001407850.1:c.4402C>T NP_001394779.1:p.Leu1468Phe missense NM_001407851.1:c.4402C>T NP_001394780.1:p.Leu1468Phe missense NM_001407852.1:c.4402C>T NP_001394781.1:p.Leu1468Phe missense NM_001407853.1:c.4402C>T NP_001394782.1:p.Leu1468Phe missense NM_001407854.1:c.4549C>T NP_001394783.1:p.Leu1517Phe missense NM_001407858.1:c.4546C>T NP_001394787.1:p.Leu1516Phe missense NM_001407859.1:c.4546C>T NP_001394788.1:p.Leu1516Phe missense NM_001407860.1:c.4546C>T NP_001394789.1:p.Leu1516Phe missense NM_001407861.1:c.4543C>T NP_001394790.1:p.Leu1515Phe missense NM_001407862.1:c.4348C>T NP_001394791.1:p.Leu1450Phe missense NM_001407863.1:c.4423C>T NP_001394792.1:p.Leu1475Phe missense NM_001407874.1:c.4342C>T NP_001394803.1:p.Leu1448Phe missense NM_001407875.1:c.4342C>T NP_001394804.1:p.Leu1448Phe missense NM_001407879.1:c.4339C>T NP_001394808.1:p.Leu1447Phe missense NM_001407881.1:c.4339C>T NP_001394810.1:p.Leu1447Phe missense NM_001407882.1:c.4339C>T NP_001394811.1:p.Leu1447Phe missense NM_001407884.1:c.4339C>T NP_001394813.1:p.Leu1447Phe missense NM_001407885.1:c.4339C>T NP_001394814.1:p.Leu1447Phe missense NM_001407886.1:c.4339C>T NP_001394815.1:p.Leu1447Phe missense NM_001407887.1:c.4339C>T NP_001394816.1:p.Leu1447Phe missense NM_001407889.1:c.4339C>T NP_001394818.1:p.Leu1447Phe missense NM_001407894.1:c.4336C>T NP_001394823.1:p.Leu1446Phe missense NM_001407895.1:c.4336C>T NP_001394824.1:p.Leu1446Phe missense NM_001407896.1:c.4336C>T NP_001394825.1:p.Leu1446Phe missense NM_001407897.1:c.4336C>T NP_001394826.1:p.Leu1446Phe missense NM_001407898.1:c.4336C>T NP_001394827.1:p.Leu1446Phe missense NM_001407899.1:c.4336C>T NP_001394828.1:p.Leu1446Phe missense NM_001407900.1:c.4336C>T NP_001394829.1:p.Leu1446Phe missense NM_001407902.1:c.4336C>T NP_001394831.1:p.Leu1446Phe missense NM_001407904.1:c.4336C>T NP_001394833.1:p.Leu1446Phe missense NM_001407906.1:c.4336C>T NP_001394835.1:p.Leu1446Phe missense NM_001407907.1:c.4336C>T NP_001394836.1:p.Leu1446Phe missense NM_001407908.1:c.4336C>T NP_001394837.1:p.Leu1446Phe missense NM_001407909.1:c.4336C>T NP_001394838.1:p.Leu1446Phe missense NM_001407910.1:c.4336C>T NP_001394839.1:p.Leu1446Phe missense NM_001407915.1:c.4333C>T NP_001394844.1:p.Leu1445Phe missense NM_001407916.1:c.4333C>T NP_001394845.1:p.Leu1445Phe missense NM_001407917.1:c.4333C>T NP_001394846.1:p.Leu1445Phe missense NM_001407918.1:c.4333C>T NP_001394847.1:p.Leu1445Phe missense NM_001407919.1:c.4426C>T NP_001394848.1:p.Leu1476Phe missense NM_001407920.1:c.4285C>T NP_001394849.1:p.Leu1429Phe missense NM_001407921.1:c.4285C>T NP_001394850.1:p.Leu1429Phe missense NM_001407922.1:c.4285C>T NP_001394851.1:p.Leu1429Phe missense NM_001407923.1:c.4285C>T NP_001394852.1:p.Leu1429Phe missense NM_001407924.1:c.4285C>T NP_001394853.1:p.Leu1429Phe missense NM_001407925.1:c.4285C>T NP_001394854.1:p.Leu1429Phe missense NM_001407926.1:c.4285C>T NP_001394855.1:p.Leu1429Phe missense NM_001407927.1:c.4282C>T NP_001394856.1:p.Leu1428Phe missense NM_001407928.1:c.4282C>T NP_001394857.1:p.Leu1428Phe missense NM_001407929.1:c.4282C>T NP_001394858.1:p.Leu1428Phe missense NM_001407930.1:c.4282C>T NP_001394859.1:p.Leu1428Phe missense NM_001407931.1:c.4282C>T NP_001394860.1:p.Leu1428Phe missense NM_001407932.1:c.4282C>T NP_001394861.1:p.Leu1428Phe missense NM_001407933.1:c.4282C>T NP_001394862.1:p.Leu1428Phe missense NM_001407934.1:c.4279C>T NP_001394863.1:p.Leu1427Phe missense NM_001407935.1:c.4279C>T NP_001394864.1:p.Leu1427Phe missense NM_001407936.1:c.4279C>T NP_001394865.1:p.Leu1427Phe missense NM_001407937.1:c.4426C>T NP_001394866.1:p.Leu1476Phe missense NM_001407938.1:c.4426C>T NP_001394867.1:p.Leu1476Phe missense NM_001407939.1:c.4423C>T NP_001394868.1:p.Leu1475Phe missense NM_001407940.1:c.4423C>T NP_001394869.1:p.Leu1475Phe missense NM_001407941.1:c.4420C>T NP_001394870.1:p.Leu1474Phe missense NM_001407942.1:c.4408C>T NP_001394871.1:p.Leu1470Phe missense NM_001407943.1:c.4405C>T NP_001394872.1:p.Leu1469Phe missense NM_001407944.1:c.4405C>T NP_001394873.1:p.Leu1469Phe missense NM_001407945.1:c.4405C>T NP_001394874.1:p.Leu1469Phe missense NM_001407946.1:c.4216C>T NP_001394875.1:p.Leu1406Phe missense NM_001407947.1:c.4216C>T NP_001394876.1:p.Leu1406Phe missense NM_001407948.1:c.4216C>T NP_001394877.1:p.Leu1406Phe missense NM_001407949.1:c.4216C>T NP_001394878.1:p.Leu1406Phe missense NM_001407950.1:c.4213C>T NP_001394879.1:p.Leu1405Phe missense NM_001407951.1:c.4213C>T NP_001394880.1:p.Leu1405Phe missense NM_001407952.1:c.4213C>T NP_001394881.1:p.Leu1405Phe missense NM_001407953.1:c.4213C>T NP_001394882.1:p.Leu1405Phe missense NM_001407954.1:c.4213C>T NP_001394883.1:p.Leu1405Phe missense NM_001407955.1:c.4213C>T NP_001394884.1:p.Leu1405Phe missense NM_001407956.1:c.4210C>T NP_001394885.1:p.Leu1404Phe missense NM_001407957.1:c.4210C>T NP_001394886.1:p.Leu1404Phe missense NM_001407958.1:c.4210C>T NP_001394887.1:p.Leu1404Phe missense NM_001407959.1:c.4168C>T NP_001394888.1:p.Leu1390Phe missense NM_001407960.1:c.4165C>T NP_001394889.1:p.Leu1389Phe missense NM_001407962.1:c.4165C>T NP_001394891.1:p.Leu1389Phe missense NM_001407963.1:c.4162C>T NP_001394892.1:p.Leu1388Phe missense NM_001407965.1:c.4042C>T NP_001394894.1:p.Leu1348Phe missense NM_001407966.1:c.3661C>T NP_001394895.1:p.Leu1221Phe missense NM_001407967.1:c.3658C>T NP_001394896.1:p.Leu1220Phe missense NM_001407968.1:c.1945C>T NP_001394897.1:p.Leu649Phe missense NM_001407969.1:c.1942C>T NP_001394898.1:p.Leu648Phe missense NM_001407970.1:c.1306C>T NP_001394899.1:p.Leu436Phe missense NM_001407971.1:c.1306C>T NP_001394900.1:p.Leu436Phe missense NM_001407972.1:c.1303C>T NP_001394901.1:p.Leu435Phe missense NM_001407973.1:c.1240C>T NP_001394902.1:p.Leu414Phe missense NM_001407974.1:c.1240C>T NP_001394903.1:p.Leu414Phe missense NM_001407975.1:c.1240C>T NP_001394904.1:p.Leu414Phe missense NM_001407976.1:c.1240C>T NP_001394905.1:p.Leu414Phe missense NM_001407977.1:c.1240C>T NP_001394906.1:p.Leu414Phe missense NM_001407978.1:c.1240C>T NP_001394907.1:p.Leu414Phe missense NM_001407979.1:c.1237C>T NP_001394908.1:p.Leu413Phe missense NM_001407980.1:c.1237C>T NP_001394909.1:p.Leu413Phe missense NM_001407981.1:c.1237C>T NP_001394910.1:p.Leu413Phe missense NM_001407982.1:c.1237C>T NP_001394911.1:p.Leu413Phe missense NM_001407983.1:c.1237C>T NP_001394912.1:p.Leu413Phe missense NM_001407984.1:c.1237C>T NP_001394913.1:p.Leu413Phe missense NM_001407985.1:c.1237C>T NP_001394914.1:p.Leu413Phe missense NM_001407986.1:c.1237C>T NP_001394915.1:p.Leu413Phe missense NM_001407990.1:c.1237C>T NP_001394919.1:p.Leu413Phe missense NM_001407991.1:c.1237C>T NP_001394920.1:p.Leu413Phe missense NM_001407992.1:c.1237C>T NP_001394921.1:p.Leu413Phe missense NM_001407993.1:c.1237C>T NP_001394922.1:p.Leu413Phe missense NM_001408392.1:c.1234C>T NP_001395321.1:p.Leu412Phe missense NM_001408396.1:c.1234C>T NP_001395325.1:p.Leu412Phe missense NM_001408397.1:c.1234C>T NP_001395326.1:p.Leu412Phe missense NM_001408398.1:c.1234C>T NP_001395327.1:p.Leu412Phe missense NM_001408399.1:c.1234C>T NP_001395328.1:p.Leu412Phe missense NM_001408400.1:c.1234C>T NP_001395329.1:p.Leu412Phe missense NM_001408401.1:c.1234C>T NP_001395330.1:p.Leu412Phe missense NM_001408402.1:c.1234C>T NP_001395331.1:p.Leu412Phe missense NM_001408403.1:c.1234C>T NP_001395332.1:p.Leu412Phe missense NM_001408404.1:c.1234C>T NP_001395333.1:p.Leu412Phe missense NM_001408406.1:c.1231C>T NP_001395335.1:p.Leu411Phe missense NM_001408407.1:c.1231C>T NP_001395336.1:p.Leu411Phe missense NM_001408408.1:c.1231C>T NP_001395337.1:p.Leu411Phe missense NM_001408409.1:c.1228C>T NP_001395338.1:p.Leu410Phe missense NM_001408410.1:c.1165C>T NP_001395339.1:p.Leu389Phe missense NM_001408411.1:c.1162C>T NP_001395340.1:p.Leu388Phe missense NM_001408412.1:c.1159C>T NP_001395341.1:p.Leu387Phe missense NM_001408413.1:c.1159C>T NP_001395342.1:p.Leu387Phe missense NM_001408414.1:c.1159C>T NP_001395343.1:p.Leu387Phe missense NM_001408415.1:c.1159C>T NP_001395344.1:p.Leu387Phe missense NM_001408416.1:c.1159C>T NP_001395345.1:p.Leu387Phe missense NM_001408418.1:c.1123C>T NP_001395347.1:p.Leu375Phe missense NM_001408419.1:c.1123C>T NP_001395348.1:p.Leu375Phe missense NM_001408420.1:c.1123C>T NP_001395349.1:p.Leu375Phe missense NM_001408421.1:c.1120C>T NP_001395350.1:p.Leu374Phe missense NM_001408422.1:c.1120C>T NP_001395351.1:p.Leu374Phe missense NM_001408423.1:c.1120C>T NP_001395352.1:p.Leu374Phe missense NM_001408424.1:c.1120C>T NP_001395353.1:p.Leu374Phe missense NM_001408425.1:c.1117C>T NP_001395354.1:p.Leu373Phe missense NM_001408426.1:c.1117C>T NP_001395355.1:p.Leu373Phe missense NM_001408427.1:c.1117C>T NP_001395356.1:p.Leu373Phe missense NM_001408428.1:c.1117C>T NP_001395357.1:p.Leu373Phe missense NM_001408429.1:c.1117C>T NP_001395358.1:p.Leu373Phe missense NM_001408430.1:c.1117C>T NP_001395359.1:p.Leu373Phe missense NM_001408431.1:c.1117C>T NP_001395360.1:p.Leu373Phe missense NM_001408432.1:c.1114C>T NP_001395361.1:p.Leu372Phe missense NM_001408433.1:c.1114C>T NP_001395362.1:p.Leu372Phe missense NM_001408434.1:c.1114C>T NP_001395363.1:p.Leu372Phe missense NM_001408435.1:c.1114C>T NP_001395364.1:p.Leu372Phe missense NM_001408436.1:c.1114C>T NP_001395365.1:p.Leu372Phe missense NM_001408437.1:c.1114C>T NP_001395366.1:p.Leu372Phe missense NM_001408438.1:c.1114C>T NP_001395367.1:p.Leu372Phe missense NM_001408439.1:c.1114C>T NP_001395368.1:p.Leu372Phe missense NM_001408440.1:c.1114C>T NP_001395369.1:p.Leu372Phe missense NM_001408441.1:c.1114C>T NP_001395370.1:p.Leu372Phe missense NM_001408442.1:c.1114C>T NP_001395371.1:p.Leu372Phe missense NM_001408443.1:c.1114C>T NP_001395372.1:p.Leu372Phe missense NM_001408444.1:c.1114C>T NP_001395373.1:p.Leu372Phe missense NM_001408445.1:c.1111C>T NP_001395374.1:p.Leu371Phe missense NM_001408446.1:c.1111C>T NP_001395375.1:p.Leu371Phe missense NM_001408447.1:c.1111C>T NP_001395376.1:p.Leu371Phe missense NM_001408448.1:c.1111C>T NP_001395377.1:p.Leu371Phe missense NM_001408450.1:c.1111C>T NP_001395379.1:p.Leu371Phe missense NM_001408451.1:c.1105C>T NP_001395380.1:p.Leu369Phe missense NM_001408452.1:c.1099C>T NP_001395381.1:p.Leu367Phe missense NM_001408453.1:c.1099C>T NP_001395382.1:p.Leu367Phe missense NM_001408454.1:c.1099C>T NP_001395383.1:p.Leu367Phe missense NM_001408455.1:c.1099C>T NP_001395384.1:p.Leu367Phe missense NM_001408456.1:c.1099C>T NP_001395385.1:p.Leu367Phe missense NM_001408457.1:c.1099C>T NP_001395386.1:p.Leu367Phe missense NM_001408458.1:c.1096C>T NP_001395387.1:p.Leu366Phe missense NM_001408459.1:c.1096C>T NP_001395388.1:p.Leu366Phe missense NM_001408460.1:c.1096C>T NP_001395389.1:p.Leu366Phe missense NM_001408461.1:c.1096C>T NP_001395390.1:p.Leu366Phe missense NM_001408462.1:c.1096C>T NP_001395391.1:p.Leu366Phe missense NM_001408463.1:c.1096C>T NP_001395392.1:p.Leu366Phe missense NM_001408464.1:c.1096C>T NP_001395393.1:p.Leu366Phe missense NM_001408465.1:c.1096C>T NP_001395394.1:p.Leu366Phe missense NM_001408466.1:c.1096C>T NP_001395395.1:p.Leu366Phe missense NM_001408467.1:c.1096C>T NP_001395396.1:p.Leu366Phe missense NM_001408468.1:c.1093C>T NP_001395397.1:p.Leu365Phe missense NM_001408469.1:c.1093C>T NP_001395398.1:p.Leu365Phe missense NM_001408470.1:c.1093C>T NP_001395399.1:p.Leu365Phe missense NM_001408472.1:c.1237C>T NP_001395401.1:p.Leu413Phe missense NM_001408473.1:c.1234C>T NP_001395402.1:p.Leu412Phe missense NM_001408474.1:c.1039C>T NP_001395403.1:p.Leu347Phe missense NM_001408475.1:c.1036C>T NP_001395404.1:p.Leu346Phe missense NM_001408476.1:c.1036C>T NP_001395405.1:p.Leu346Phe missense NM_001408478.1:c.1030C>T NP_001395407.1:p.Leu344Phe missense NM_001408479.1:c.1030C>T NP_001395408.1:p.Leu344Phe missense NM_001408480.1:c.1030C>T NP_001395409.1:p.Leu344Phe missense NM_001408481.1:c.1027C>T NP_001395410.1:p.Leu343Phe missense NM_001408482.1:c.1027C>T NP_001395411.1:p.Leu343Phe missense NM_001408483.1:c.1027C>T NP_001395412.1:p.Leu343Phe missense NM_001408484.1:c.1027C>T NP_001395413.1:p.Leu343Phe missense NM_001408485.1:c.1027C>T NP_001395414.1:p.Leu343Phe missense NM_001408489.1:c.1027C>T NP_001395418.1:p.Leu343Phe missense NM_001408490.1:c.1027C>T NP_001395419.1:p.Leu343Phe missense NM_001408491.1:c.1027C>T NP_001395420.1:p.Leu343Phe missense NM_001408492.1:c.1024C>T NP_001395421.1:p.Leu342Phe missense NM_001408493.1:c.1024C>T NP_001395422.1:p.Leu342Phe missense NM_001408494.1:c.1000C>T NP_001395423.1:p.Leu334Phe missense NM_001408495.1:c.994C>T NP_001395424.1:p.Leu332Phe missense NM_001408496.1:c.976C>T NP_001395425.1:p.Leu326Phe missense NM_001408497.1:c.976C>T NP_001395426.1:p.Leu326Phe missense NM_001408498.1:c.976C>T NP_001395427.1:p.Leu326Phe missense NM_001408499.1:c.976C>T NP_001395428.1:p.Leu326Phe missense NM_001408500.1:c.976C>T NP_001395429.1:p.Leu326Phe missense NM_001408501.1:c.976C>T NP_001395430.1:p.Leu326Phe missense NM_001408502.1:c.973C>T NP_001395431.1:p.Leu325Phe missense NM_001408503.1:c.973C>T NP_001395432.1:p.Leu325Phe missense NM_001408504.1:c.973C>T NP_001395433.1:p.Leu325Phe missense NM_001408505.1:c.970C>T NP_001395434.1:p.Leu324Phe missense NM_001408506.1:c.913C>T NP_001395435.1:p.Leu305Phe missense NM_001408507.1:c.910C>T NP_001395436.1:p.Leu304Phe missense NM_001408508.1:c.901C>T NP_001395437.1:p.Leu301Phe missense NM_001408509.1:c.898C>T NP_001395438.1:p.Leu300Phe missense NM_001408510.1:c.859C>T NP_001395439.1:p.Leu287Phe missense NM_001408511.1:c.856C>T NP_001395440.1:p.Leu286Phe missense NM_001408512.1:c.736C>T NP_001395441.1:p.Leu246Phe missense NM_007297.4:c.4408C>T NP_009228.2:p.Leu1470Phe missense NM_007298.4:c.1237C>T NP_009229.2:p.Leu413Phe missense NM_007299.4:c.1237C>T NP_009230.2:p.Leu413Phe missense NM_007300.4:c.4612C>T NP_009231.2:p.Leu1538Phe missense NM_007304.2:c.1237C>T NP_009235.2:p.Leu413Phe missense NR_027676.2:n.4726C>T non-coding transcript variant NC_000017.11:g.43074457G>A NC_000017.10:g.41226474G>A NG_005905.2:g.143527C>T LRG_292:g.143527C>T LRG_292t1:c.4549C>T LRG_292p1:p.Leu1517Phe - Protein change
- L1538F, L1470F, L1517F, L413F, L1220F, L1348F, L1445F, L1468F, L1490F, L1491F, L1514F, L1515F, L1537F, L286F, L342F, L346F, L388F, L436F, L649F, L1390F, L1405F, L1406F, L1428F, L1446F, L1447F, L1469F, L1474F, L1475F, L1476F, L1497F, L1498F, L1539F, L246F, L301F, L326F, L347F, L369F, L371F, L375F, L387F, L411F, L435F, L648F, L1221F, L1388F, L1450F, L1513F, L300F, L305F, L324F, L325F, L332F, L334F, L344F, L367F, L374F, L410F, L414F, L1389F, L1404F, L1427F, L1429F, L1448F, L1473F, L1489F, L1512F, L1516F, L287F, L304F, L343F, L365F, L366F, L372F, L373F, L389F, L412F
- Other names
- -
- Canonical SPDI
- NC_000017.11:43074456: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), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
- 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
|
Sep 26, 2018 | RCV000818666.8 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Mar 22, 2022 | RCV002336698.2 |
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
(Sep 26, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000959291.4
First in ClinVar: Aug 14, 2019 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA1-related disease. This variant is present in population databases (rs137894496, ExAC 0.009%). This sequence change replaces leucine with phenylalanine at codon 1517 of the BRCA1 protein (p.Leu1517Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. (less)
|
|
|
Uncertain significance
(Mar 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002640165.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.L1517F variant (also known as c.4549C>T), located in coding exon 13 of the BRCA1 gene, results from a C to T substitution at nucleotide … (more)
The p.L1517F variant (also known as c.4549C>T), located in coding exon 13 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4549. The leucine at codon 1517 is replaced by phenylalanine, an amino acid with highly similar properties. This variant had 132.21% of wildtype activity in a transcription activation assay (Woods NT et al. NPJ Genom Med, 2016 Mar;1:). This amino acid position is 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)
|
Comment:
Comment:
The p.L1517F variant (also known as c.4549C>T), located in coding exon 13 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4549. The leucine at codon 1517 is replaced by phenylalanine, an amino acid with highly similar properties. This variant had 132.21% of wildtype activity in a transcription activation assay (Woods NT et al. NPJ Genom Med, 2016 Mar;1:). This amino acid position is 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.
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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA1-related disease. This variant is present in population databases (rs137894496, ExAC 0.009%). This sequence change replaces leucine with phenylalanine at codon 1517 of the BRCA1 protein (p.Leu1517Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine.
Comment:
The p.L1517F variant (also known as c.4549C>T), located in coding exon 13 of the BRCA1 gene, results from a C to T substitution at nucleotide position 4549. The leucine at codon 1517 is replaced by phenylalanine, an amino acid with highly similar properties. This variant had 132.21% of wildtype activity in a transcription activation assay (Woods NT et al. NPJ Genom Med, 2016 Mar;1:). This amino acid position is 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.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance. | Woods NT | NPJ genomic medicine | 2016 | PMID: 28781887 |
Text-mined citations for rs137894496 ...
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.