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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 578485). This missense change has been observed in individual(s) with breast cancer (PMID: 29470806). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1392 of the BRCA1 protein (p.Leu1392Ser).
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4175T>C (p.Leu1392Ser)
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.4175T>C (p.Leu1392Ser)
Variation ID: 578485 Accession: VCV000578485.9
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43090954 (GRCh38) [ NCBI UCSC ] 17: 41242971 (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 Oct 10, 2018 May 1, 2024 Sep 16, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4175T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Leu1392Ser missense NM_001407571.1:c.3962T>C NP_001394500.1:p.Leu1321Ser missense NM_001407581.1:c.4175T>C NP_001394510.1:p.Leu1392Ser missense NM_001407582.1:c.4175T>C NP_001394511.1:p.Leu1392Ser missense NM_001407583.1:c.4175T>C NP_001394512.1:p.Leu1392Ser missense NM_001407585.1:c.4175T>C NP_001394514.1:p.Leu1392Ser missense NM_001407587.1:c.4172T>C NP_001394516.1:p.Leu1391Ser missense NM_001407590.1:c.4172T>C NP_001394519.1:p.Leu1391Ser missense NM_001407591.1:c.4172T>C NP_001394520.1:p.Leu1391Ser missense NM_001407593.1:c.4175T>C NP_001394522.1:p.Leu1392Ser missense NM_001407594.1:c.4175T>C NP_001394523.1:p.Leu1392Ser missense NM_001407596.1:c.4175T>C NP_001394525.1:p.Leu1392Ser missense NM_001407597.1:c.4175T>C NP_001394526.1:p.Leu1392Ser missense NM_001407598.1:c.4175T>C NP_001394527.1:p.Leu1392Ser missense NM_001407602.1:c.4175T>C NP_001394531.1:p.Leu1392Ser missense NM_001407603.1:c.4175T>C NP_001394532.1:p.Leu1392Ser missense NM_001407605.1:c.4175T>C NP_001394534.1:p.Leu1392Ser missense NM_001407610.1:c.4172T>C NP_001394539.1:p.Leu1391Ser missense NM_001407611.1:c.4172T>C NP_001394540.1:p.Leu1391Ser missense NM_001407612.1:c.4172T>C NP_001394541.1:p.Leu1391Ser missense NM_001407613.1:c.4172T>C NP_001394542.1:p.Leu1391Ser missense NM_001407614.1:c.4172T>C NP_001394543.1:p.Leu1391Ser missense NM_001407615.1:c.4172T>C NP_001394544.1:p.Leu1391Ser missense NM_001407616.1:c.4175T>C NP_001394545.1:p.Leu1392Ser missense NM_001407617.1:c.4175T>C NP_001394546.1:p.Leu1392Ser missense NM_001407618.1:c.4175T>C NP_001394547.1:p.Leu1392Ser missense NM_001407619.1:c.4175T>C NP_001394548.1:p.Leu1392Ser missense NM_001407620.1:c.4175T>C NP_001394549.1:p.Leu1392Ser missense NM_001407621.1:c.4175T>C NP_001394550.1:p.Leu1392Ser missense NM_001407622.1:c.4175T>C NP_001394551.1:p.Leu1392Ser missense NM_001407623.1:c.4175T>C NP_001394552.1:p.Leu1392Ser missense NM_001407624.1:c.4175T>C NP_001394553.1:p.Leu1392Ser missense NM_001407625.1:c.4175T>C NP_001394554.1:p.Leu1392Ser missense NM_001407626.1:c.4175T>C NP_001394555.1:p.Leu1392Ser missense NM_001407627.1:c.4172T>C NP_001394556.1:p.Leu1391Ser missense NM_001407628.1:c.4172T>C NP_001394557.1:p.Leu1391Ser missense NM_001407629.1:c.4172T>C NP_001394558.1:p.Leu1391Ser missense NM_001407630.1:c.4172T>C NP_001394559.1:p.Leu1391Ser missense NM_001407631.1:c.4172T>C NP_001394560.1:p.Leu1391Ser missense NM_001407632.1:c.4172T>C NP_001394561.1:p.Leu1391Ser missense NM_001407633.1:c.4172T>C NP_001394562.1:p.Leu1391Ser missense NM_001407634.1:c.4172T>C NP_001394563.1:p.Leu1391Ser missense NM_001407635.1:c.4172T>C NP_001394564.1:p.Leu1391Ser missense NM_001407636.1:c.4172T>C NP_001394565.1:p.Leu1391Ser missense NM_001407637.1:c.4172T>C NP_001394566.1:p.Leu1391Ser missense NM_001407638.1:c.4172T>C NP_001394567.1:p.Leu1391Ser missense NM_001407639.1:c.4175T>C NP_001394568.1:p.Leu1392Ser missense NM_001407640.1:c.4175T>C NP_001394569.1:p.Leu1392Ser missense NM_001407641.1:c.4175T>C NP_001394570.1:p.Leu1392Ser missense NM_001407642.1:c.4175T>C NP_001394571.1:p.Leu1392Ser missense NM_001407644.1:c.4172T>C NP_001394573.1:p.Leu1391Ser missense NM_001407645.1:c.4172T>C NP_001394574.1:p.Leu1391Ser missense NM_001407646.1:c.4166T>C NP_001394575.1:p.Leu1389Ser missense NM_001407647.1:c.4166T>C NP_001394576.1:p.Leu1389Ser missense NM_001407648.1:c.4052T>C NP_001394577.1:p.Leu1351Ser missense NM_001407649.1:c.4049T>C NP_001394578.1:p.Leu1350Ser missense NM_001407652.1:c.4175T>C NP_001394581.1:p.Leu1392Ser missense NM_001407653.1:c.4097T>C NP_001394582.1:p.Leu1366Ser missense NM_001407654.1:c.4097T>C NP_001394583.1:p.Leu1366Ser missense NM_001407655.1:c.4097T>C NP_001394584.1:p.Leu1366Ser missense NM_001407656.1:c.4097T>C NP_001394585.1:p.Leu1366Ser missense NM_001407657.1:c.4097T>C NP_001394586.1:p.Leu1366Ser missense NM_001407658.1:c.4097T>C NP_001394587.1:p.Leu1366Ser missense NM_001407659.1:c.4094T>C NP_001394588.1:p.Leu1365Ser missense NM_001407660.1:c.4094T>C NP_001394589.1:p.Leu1365Ser missense NM_001407661.1:c.4094T>C NP_001394590.1:p.Leu1365Ser missense NM_001407662.1:c.4094T>C NP_001394591.1:p.Leu1365Ser missense NM_001407663.1:c.4097T>C NP_001394592.1:p.Leu1366Ser missense NM_001407664.1:c.4052T>C NP_001394593.1:p.Leu1351Ser missense NM_001407665.1:c.4052T>C NP_001394594.1:p.Leu1351Ser missense NM_001407666.1:c.4052T>C NP_001394595.1:p.Leu1351Ser missense NM_001407667.1:c.4052T>C NP_001394596.1:p.Leu1351Ser missense NM_001407668.1:c.4052T>C NP_001394597.1:p.Leu1351Ser missense NM_001407669.1:c.4052T>C NP_001394598.1:p.Leu1351Ser missense NM_001407670.1:c.4049T>C NP_001394599.1:p.Leu1350Ser missense NM_001407671.1:c.4049T>C NP_001394600.1:p.Leu1350Ser missense NM_001407672.1:c.4049T>C NP_001394601.1:p.Leu1350Ser missense NM_001407673.1:c.4049T>C NP_001394602.1:p.Leu1350Ser missense NM_001407674.1:c.4052T>C NP_001394603.1:p.Leu1351Ser missense NM_001407675.1:c.4052T>C NP_001394604.1:p.Leu1351Ser missense NM_001407676.1:c.4052T>C NP_001394605.1:p.Leu1351Ser missense NM_001407677.1:c.4052T>C NP_001394606.1:p.Leu1351Ser missense NM_001407678.1:c.4052T>C NP_001394607.1:p.Leu1351Ser missense NM_001407679.1:c.4052T>C NP_001394608.1:p.Leu1351Ser missense NM_001407680.1:c.4052T>C NP_001394609.1:p.Leu1351Ser missense NM_001407681.1:c.4052T>C NP_001394610.1:p.Leu1351Ser missense NM_001407682.1:c.4052T>C NP_001394611.1:p.Leu1351Ser missense NM_001407683.1:c.4052T>C NP_001394612.1:p.Leu1351Ser missense NM_001407684.1:c.4175T>C NP_001394613.1:p.Leu1392Ser missense NM_001407685.1:c.4049T>C NP_001394614.1:p.Leu1350Ser missense NM_001407686.1:c.4049T>C NP_001394615.1:p.Leu1350Ser missense NM_001407687.1:c.4049T>C NP_001394616.1:p.Leu1350Ser missense NM_001407688.1:c.4049T>C NP_001394617.1:p.Leu1350Ser missense NM_001407689.1:c.4049T>C NP_001394618.1:p.Leu1350Ser missense NM_001407690.1:c.4049T>C NP_001394619.1:p.Leu1350Ser missense NM_001407691.1:c.4049T>C NP_001394620.1:p.Leu1350Ser missense NM_001407692.1:c.4034T>C NP_001394621.1:p.Leu1345Ser missense NM_001407694.1:c.4034T>C NP_001394623.1:p.Leu1345Ser missense NM_001407695.1:c.4034T>C NP_001394624.1:p.Leu1345Ser missense NM_001407696.1:c.4034T>C NP_001394625.1:p.Leu1345Ser missense NM_001407697.1:c.4034T>C NP_001394626.1:p.Leu1345Ser missense NM_001407698.1:c.4034T>C NP_001394627.1:p.Leu1345Ser missense NM_001407724.1:c.4034T>C NP_001394653.1:p.Leu1345Ser missense NM_001407725.1:c.4034T>C NP_001394654.1:p.Leu1345Ser missense NM_001407726.1:c.4034T>C NP_001394655.1:p.Leu1345Ser missense NM_001407727.1:c.4034T>C NP_001394656.1:p.Leu1345Ser missense NM_001407728.1:c.4034T>C NP_001394657.1:p.Leu1345Ser missense NM_001407729.1:c.4034T>C NP_001394658.1:p.Leu1345Ser missense NM_001407730.1:c.4034T>C NP_001394659.1:p.Leu1345Ser missense NM_001407731.1:c.4034T>C NP_001394660.1:p.Leu1345Ser missense NM_001407732.1:c.4034T>C NP_001394661.1:p.Leu1345Ser missense NM_001407733.1:c.4034T>C NP_001394662.1:p.Leu1345Ser missense NM_001407734.1:c.4034T>C NP_001394663.1:p.Leu1345Ser missense NM_001407735.1:c.4034T>C NP_001394664.1:p.Leu1345Ser missense NM_001407736.1:c.4034T>C NP_001394665.1:p.Leu1345Ser missense NM_001407737.1:c.4034T>C NP_001394666.1:p.Leu1345Ser missense NM_001407738.1:c.4034T>C NP_001394667.1:p.Leu1345Ser missense NM_001407739.1:c.4034T>C NP_001394668.1:p.Leu1345Ser missense NM_001407740.1:c.4031T>C NP_001394669.1:p.Leu1344Ser missense NM_001407741.1:c.4031T>C NP_001394670.1:p.Leu1344Ser missense NM_001407742.1:c.4031T>C NP_001394671.1:p.Leu1344Ser missense NM_001407743.1:c.4031T>C NP_001394672.1:p.Leu1344Ser missense NM_001407744.1:c.4031T>C NP_001394673.1:p.Leu1344Ser missense NM_001407745.1:c.4031T>C NP_001394674.1:p.Leu1344Ser missense NM_001407746.1:c.4031T>C NP_001394675.1:p.Leu1344Ser missense NM_001407747.1:c.4031T>C NP_001394676.1:p.Leu1344Ser missense NM_001407748.1:c.4031T>C NP_001394677.1:p.Leu1344Ser missense NM_001407749.1:c.4031T>C NP_001394678.1:p.Leu1344Ser missense NM_001407750.1:c.4034T>C NP_001394679.1:p.Leu1345Ser missense NM_001407751.1:c.4034T>C NP_001394680.1:p.Leu1345Ser missense NM_001407752.1:c.4034T>C NP_001394681.1:p.Leu1345Ser missense NM_001407838.1:c.4031T>C NP_001394767.1:p.Leu1344Ser missense NM_001407839.1:c.4031T>C NP_001394768.1:p.Leu1344Ser missense NM_001407841.1:c.4031T>C NP_001394770.1:p.Leu1344Ser missense NM_001407842.1:c.4031T>C NP_001394771.1:p.Leu1344Ser missense NM_001407843.1:c.4031T>C NP_001394772.1:p.Leu1344Ser missense NM_001407844.1:c.4031T>C NP_001394773.1:p.Leu1344Ser missense NM_001407845.1:c.4031T>C NP_001394774.1:p.Leu1344Ser missense NM_001407846.1:c.4031T>C NP_001394775.1:p.Leu1344Ser missense NM_001407847.1:c.4031T>C NP_001394776.1:p.Leu1344Ser missense NM_001407848.1:c.4031T>C NP_001394777.1:p.Leu1344Ser missense NM_001407849.1:c.4031T>C NP_001394778.1:p.Leu1344Ser missense NM_001407850.1:c.4034T>C NP_001394779.1:p.Leu1345Ser missense NM_001407851.1:c.4034T>C NP_001394780.1:p.Leu1345Ser missense NM_001407852.1:c.4034T>C NP_001394781.1:p.Leu1345Ser missense NM_001407853.1:c.3962T>C NP_001394782.1:p.Leu1321Ser missense NM_001407854.1:c.4175T>C NP_001394783.1:p.Leu1392Ser missense NM_001407858.1:c.4175T>C NP_001394787.1:p.Leu1392Ser missense NM_001407859.1:c.4175T>C NP_001394788.1:p.Leu1392Ser missense NM_001407860.1:c.4172T>C NP_001394789.1:p.Leu1391Ser missense NM_001407861.1:c.4172T>C NP_001394790.1:p.Leu1391Ser missense NM_001407862.1:c.3974T>C NP_001394791.1:p.Leu1325Ser missense NM_001407863.1:c.4052T>C NP_001394792.1:p.Leu1351Ser missense NM_001407874.1:c.3971T>C NP_001394803.1:p.Leu1324Ser missense NM_001407875.1:c.3971T>C NP_001394804.1:p.Leu1324Ser missense NM_001407879.1:c.3965T>C NP_001394808.1:p.Leu1322Ser missense NM_001407881.1:c.3965T>C NP_001394810.1:p.Leu1322Ser missense NM_001407882.1:c.3965T>C NP_001394811.1:p.Leu1322Ser missense NM_001407884.1:c.3965T>C NP_001394813.1:p.Leu1322Ser missense NM_001407885.1:c.3965T>C NP_001394814.1:p.Leu1322Ser missense NM_001407886.1:c.3965T>C NP_001394815.1:p.Leu1322Ser missense NM_001407887.1:c.3965T>C NP_001394816.1:p.Leu1322Ser missense NM_001407889.1:c.3965T>C NP_001394818.1:p.Leu1322Ser missense NM_001407894.1:c.3962T>C NP_001394823.1:p.Leu1321Ser missense NM_001407895.1:c.3962T>C NP_001394824.1:p.Leu1321Ser missense NM_001407896.1:c.3962T>C NP_001394825.1:p.Leu1321Ser missense NM_001407897.1:c.3962T>C NP_001394826.1:p.Leu1321Ser missense NM_001407898.1:c.3962T>C NP_001394827.1:p.Leu1321Ser missense NM_001407899.1:c.3962T>C NP_001394828.1:p.Leu1321Ser missense NM_001407900.1:c.3965T>C NP_001394829.1:p.Leu1322Ser missense NM_001407902.1:c.3965T>C NP_001394831.1:p.Leu1322Ser missense NM_001407904.1:c.3965T>C NP_001394833.1:p.Leu1322Ser missense NM_001407906.1:c.3965T>C NP_001394835.1:p.Leu1322Ser missense NM_001407907.1:c.3965T>C NP_001394836.1:p.Leu1322Ser missense NM_001407908.1:c.3965T>C NP_001394837.1:p.Leu1322Ser missense NM_001407909.1:c.3965T>C NP_001394838.1:p.Leu1322Ser missense NM_001407910.1:c.3965T>C NP_001394839.1:p.Leu1322Ser missense NM_001407915.1:c.3962T>C NP_001394844.1:p.Leu1321Ser missense NM_001407916.1:c.3962T>C NP_001394845.1:p.Leu1321Ser missense NM_001407917.1:c.3962T>C NP_001394846.1:p.Leu1321Ser missense NM_001407918.1:c.3962T>C NP_001394847.1:p.Leu1321Ser missense NM_001407919.1:c.4052T>C NP_001394848.1:p.Leu1351Ser missense NM_001407920.1:c.3911T>C NP_001394849.1:p.Leu1304Ser missense NM_001407921.1:c.3911T>C NP_001394850.1:p.Leu1304Ser missense NM_001407922.1:c.3911T>C NP_001394851.1:p.Leu1304Ser missense NM_001407923.1:c.3911T>C NP_001394852.1:p.Leu1304Ser missense NM_001407924.1:c.3911T>C NP_001394853.1:p.Leu1304Ser missense NM_001407925.1:c.3911T>C NP_001394854.1:p.Leu1304Ser missense NM_001407926.1:c.3911T>C NP_001394855.1:p.Leu1304Ser missense NM_001407927.1:c.3911T>C NP_001394856.1:p.Leu1304Ser missense NM_001407928.1:c.3911T>C NP_001394857.1:p.Leu1304Ser missense NM_001407929.1:c.3911T>C NP_001394858.1:p.Leu1304Ser missense NM_001407930.1:c.3908T>C NP_001394859.1:p.Leu1303Ser missense NM_001407931.1:c.3908T>C NP_001394860.1:p.Leu1303Ser missense NM_001407932.1:c.3908T>C NP_001394861.1:p.Leu1303Ser missense NM_001407933.1:c.3911T>C NP_001394862.1:p.Leu1304Ser missense NM_001407934.1:c.3908T>C NP_001394863.1:p.Leu1303Ser missense NM_001407935.1:c.3911T>C NP_001394864.1:p.Leu1304Ser missense NM_001407936.1:c.3908T>C NP_001394865.1:p.Leu1303Ser missense NM_001407937.1:c.4052T>C NP_001394866.1:p.Leu1351Ser missense NM_001407938.1:c.4052T>C NP_001394867.1:p.Leu1351Ser missense NM_001407939.1:c.4052T>C NP_001394868.1:p.Leu1351Ser missense NM_001407940.1:c.4049T>C NP_001394869.1:p.Leu1350Ser missense NM_001407941.1:c.4049T>C NP_001394870.1:p.Leu1350Ser missense NM_001407942.1:c.4034T>C NP_001394871.1:p.Leu1345Ser missense NM_001407943.1:c.4031T>C NP_001394872.1:p.Leu1344Ser missense NM_001407944.1:c.4034T>C NP_001394873.1:p.Leu1345Ser missense NM_001407945.1:c.4034T>C NP_001394874.1:p.Leu1345Ser missense NM_001407946.1:c.3842T>C NP_001394875.1:p.Leu1281Ser missense NM_001407947.1:c.3842T>C NP_001394876.1:p.Leu1281Ser missense NM_001407948.1:c.3842T>C NP_001394877.1:p.Leu1281Ser missense NM_001407949.1:c.3842T>C NP_001394878.1:p.Leu1281Ser missense NM_001407950.1:c.3842T>C NP_001394879.1:p.Leu1281Ser missense NM_001407951.1:c.3842T>C NP_001394880.1:p.Leu1281Ser missense NM_001407952.1:c.3842T>C NP_001394881.1:p.Leu1281Ser missense NM_001407953.1:c.3842T>C NP_001394882.1:p.Leu1281Ser missense NM_001407954.1:c.3839T>C NP_001394883.1:p.Leu1280Ser missense NM_001407955.1:c.3839T>C NP_001394884.1:p.Leu1280Ser missense NM_001407956.1:c.3839T>C NP_001394885.1:p.Leu1280Ser missense NM_001407957.1:c.3842T>C NP_001394886.1:p.Leu1281Ser missense NM_001407958.1:c.3839T>C NP_001394887.1:p.Leu1280Ser missense NM_001407959.1:c.3794T>C NP_001394888.1:p.Leu1265Ser missense NM_001407960.1:c.3794T>C NP_001394889.1:p.Leu1265Ser missense NM_001407962.1:c.3791T>C NP_001394891.1:p.Leu1264Ser missense NM_001407963.1:c.3794T>C NP_001394892.1:p.Leu1265Ser missense NM_001407964.1:c.4031T>C NP_001394893.1:p.Leu1344Ser missense NM_001407965.1:c.3671T>C NP_001394894.1:p.Leu1224Ser missense NM_001407966.1:c.3287T>C NP_001394895.1:p.Leu1096Ser missense NM_001407967.1:c.3287T>C NP_001394896.1:p.Leu1096Ser missense NM_001407968.1:c.1571T>C NP_001394897.1:p.Leu524Ser missense NM_001407969.1:c.1571T>C NP_001394898.1:p.Leu524Ser missense NM_001407970.1:c.866T>C NP_001394899.1:p.Leu289Ser missense NM_001407971.1:c.866T>C NP_001394900.1:p.Leu289Ser missense NM_001407972.1:c.863T>C NP_001394901.1:p.Leu288Ser missense NM_001407973.1:c.866T>C NP_001394902.1:p.Leu289Ser missense NM_001407974.1:c.866T>C NP_001394903.1:p.Leu289Ser missense NM_001407975.1:c.866T>C NP_001394904.1:p.Leu289Ser missense NM_001407976.1:c.866T>C NP_001394905.1:p.Leu289Ser missense NM_001407977.1:c.866T>C NP_001394906.1:p.Leu289Ser missense NM_001407978.1:c.866T>C NP_001394907.1:p.Leu289Ser missense NM_001407979.1:c.866T>C NP_001394908.1:p.Leu289Ser missense NM_001407980.1:c.866T>C NP_001394909.1:p.Leu289Ser missense NM_001407981.1:c.866T>C NP_001394910.1:p.Leu289Ser missense NM_001407982.1:c.866T>C NP_001394911.1:p.Leu289Ser missense NM_001407983.1:c.866T>C NP_001394912.1:p.Leu289Ser missense NM_001407984.1:c.863T>C NP_001394913.1:p.Leu288Ser missense NM_001407985.1:c.863T>C NP_001394914.1:p.Leu288Ser missense NM_001407986.1:c.863T>C NP_001394915.1:p.Leu288Ser missense NM_001407990.1:c.866T>C NP_001394919.1:p.Leu289Ser missense NM_001407991.1:c.863T>C NP_001394920.1:p.Leu288Ser missense NM_001407992.1:c.863T>C NP_001394921.1:p.Leu288Ser missense NM_001407993.1:c.866T>C NP_001394922.1:p.Leu289Ser missense NM_001408392.1:c.863T>C NP_001395321.1:p.Leu288Ser missense NM_001408396.1:c.863T>C NP_001395325.1:p.Leu288Ser missense NM_001408397.1:c.863T>C NP_001395326.1:p.Leu288Ser missense NM_001408398.1:c.863T>C NP_001395327.1:p.Leu288Ser missense NM_001408399.1:c.863T>C NP_001395328.1:p.Leu288Ser missense NM_001408400.1:c.863T>C NP_001395329.1:p.Leu288Ser missense NM_001408401.1:c.863T>C NP_001395330.1:p.Leu288Ser missense NM_001408402.1:c.863T>C NP_001395331.1:p.Leu288Ser missense NM_001408403.1:c.866T>C NP_001395332.1:p.Leu289Ser missense NM_001408404.1:c.866T>C NP_001395333.1:p.Leu289Ser missense NM_001408406.1:c.860T>C NP_001395335.1:p.Leu287Ser missense NM_001408407.1:c.863T>C NP_001395336.1:p.Leu288Ser missense NM_001408408.1:c.857T>C NP_001395337.1:p.Leu286Ser missense NM_001408409.1:c.788T>C NP_001395338.1:p.Leu263Ser missense NM_001408410.1:c.725T>C NP_001395339.1:p.Leu242Ser missense NM_001408411.1:c.788T>C NP_001395340.1:p.Leu263Ser missense NM_001408412.1:c.788T>C NP_001395341.1:p.Leu263Ser missense NM_001408413.1:c.785T>C NP_001395342.1:p.Leu262Ser missense NM_001408414.1:c.788T>C NP_001395343.1:p.Leu263Ser missense NM_001408415.1:c.788T>C NP_001395344.1:p.Leu263Ser missense NM_001408416.1:c.785T>C NP_001395345.1:p.Leu262Ser missense NM_001408418.1:c.749T>C NP_001395347.1:p.Leu250Ser missense NM_001408419.1:c.749T>C NP_001395348.1:p.Leu250Ser missense NM_001408420.1:c.749T>C NP_001395349.1:p.Leu250Ser missense NM_001408421.1:c.746T>C NP_001395350.1:p.Leu249Ser missense NM_001408422.1:c.749T>C NP_001395351.1:p.Leu250Ser missense NM_001408423.1:c.749T>C NP_001395352.1:p.Leu250Ser missense NM_001408424.1:c.746T>C NP_001395353.1:p.Leu249Ser missense NM_001408425.1:c.743T>C NP_001395354.1:p.Leu248Ser missense NM_001408426.1:c.743T>C NP_001395355.1:p.Leu248Ser missense NM_001408427.1:c.743T>C NP_001395356.1:p.Leu248Ser missense NM_001408428.1:c.743T>C NP_001395357.1:p.Leu248Ser missense NM_001408429.1:c.743T>C NP_001395358.1:p.Leu248Ser missense NM_001408430.1:c.743T>C NP_001395359.1:p.Leu248Ser missense NM_001408431.1:c.746T>C NP_001395360.1:p.Leu249Ser missense NM_001408432.1:c.740T>C NP_001395361.1:p.Leu247Ser missense NM_001408433.1:c.740T>C NP_001395362.1:p.Leu247Ser missense NM_001408434.1:c.740T>C NP_001395363.1:p.Leu247Ser missense NM_001408435.1:c.740T>C NP_001395364.1:p.Leu247Ser missense NM_001408436.1:c.743T>C NP_001395365.1:p.Leu248Ser missense NM_001408437.1:c.743T>C NP_001395366.1:p.Leu248Ser missense NM_001408438.1:c.743T>C NP_001395367.1:p.Leu248Ser missense NM_001408439.1:c.743T>C NP_001395368.1:p.Leu248Ser missense NM_001408440.1:c.743T>C NP_001395369.1:p.Leu248Ser missense NM_001408441.1:c.743T>C NP_001395370.1:p.Leu248Ser missense NM_001408442.1:c.743T>C NP_001395371.1:p.Leu248Ser missense NM_001408443.1:c.743T>C NP_001395372.1:p.Leu248Ser missense NM_001408444.1:c.743T>C NP_001395373.1:p.Leu248Ser missense NM_001408445.1:c.740T>C NP_001395374.1:p.Leu247Ser missense NM_001408446.1:c.740T>C NP_001395375.1:p.Leu247Ser missense NM_001408447.1:c.740T>C NP_001395376.1:p.Leu247Ser missense NM_001408448.1:c.740T>C NP_001395377.1:p.Leu247Ser missense NM_001408450.1:c.740T>C NP_001395379.1:p.Leu247Ser missense NM_001408451.1:c.731T>C NP_001395380.1:p.Leu244Ser missense NM_001408452.1:c.725T>C NP_001395381.1:p.Leu242Ser missense NM_001408453.1:c.725T>C NP_001395382.1:p.Leu242Ser missense NM_001408454.1:c.725T>C NP_001395383.1:p.Leu242Ser missense NM_001408455.1:c.725T>C NP_001395384.1:p.Leu242Ser missense NM_001408456.1:c.725T>C NP_001395385.1:p.Leu242Ser missense NM_001408457.1:c.725T>C NP_001395386.1:p.Leu242Ser missense NM_001408458.1:c.725T>C NP_001395387.1:p.Leu242Ser missense NM_001408459.1:c.725T>C NP_001395388.1:p.Leu242Ser missense NM_001408460.1:c.725T>C NP_001395389.1:p.Leu242Ser missense NM_001408461.1:c.725T>C NP_001395390.1:p.Leu242Ser missense NM_001408462.1:c.722T>C NP_001395391.1:p.Leu241Ser missense NM_001408463.1:c.722T>C NP_001395392.1:p.Leu241Ser missense NM_001408464.1:c.722T>C NP_001395393.1:p.Leu241Ser missense NM_001408465.1:c.722T>C NP_001395394.1:p.Leu241Ser missense NM_001408466.1:c.725T>C NP_001395395.1:p.Leu242Ser missense NM_001408467.1:c.725T>C NP_001395396.1:p.Leu242Ser missense NM_001408468.1:c.722T>C NP_001395397.1:p.Leu241Ser missense NM_001408469.1:c.725T>C NP_001395398.1:p.Leu242Ser missense NM_001408470.1:c.722T>C NP_001395399.1:p.Leu241Ser missense NM_001408472.1:c.866T>C NP_001395401.1:p.Leu289Ser missense NM_001408473.1:c.863T>C NP_001395402.1:p.Leu288Ser missense NM_001408474.1:c.665T>C NP_001395403.1:p.Leu222Ser missense NM_001408475.1:c.662T>C NP_001395404.1:p.Leu221Ser missense NM_001408476.1:c.665T>C NP_001395405.1:p.Leu222Ser missense NM_001408478.1:c.656T>C NP_001395407.1:p.Leu219Ser missense NM_001408479.1:c.656T>C NP_001395408.1:p.Leu219Ser missense NM_001408480.1:c.656T>C NP_001395409.1:p.Leu219Ser missense NM_001408481.1:c.656T>C NP_001395410.1:p.Leu219Ser missense NM_001408482.1:c.656T>C NP_001395411.1:p.Leu219Ser missense NM_001408483.1:c.656T>C NP_001395412.1:p.Leu219Ser missense NM_001408484.1:c.656T>C NP_001395413.1:p.Leu219Ser missense NM_001408485.1:c.656T>C NP_001395414.1:p.Leu219Ser missense NM_001408489.1:c.656T>C NP_001395418.1:p.Leu219Ser missense NM_001408490.1:c.653T>C NP_001395419.1:p.Leu218Ser missense NM_001408491.1:c.653T>C NP_001395420.1:p.Leu218Ser missense NM_001408492.1:c.656T>C NP_001395421.1:p.Leu219Ser missense NM_001408493.1:c.653T>C NP_001395422.1:p.Leu218Ser missense NM_001408494.1:c.626T>C NP_001395423.1:p.Leu209Ser missense NM_001408495.1:c.623T>C NP_001395424.1:p.Leu208Ser missense NM_001408496.1:c.602T>C NP_001395425.1:p.Leu201Ser missense NM_001408497.1:c.602T>C NP_001395426.1:p.Leu201Ser missense NM_001408498.1:c.602T>C NP_001395427.1:p.Leu201Ser missense NM_001408499.1:c.602T>C NP_001395428.1:p.Leu201Ser missense NM_001408500.1:c.602T>C NP_001395429.1:p.Leu201Ser missense NM_001408501.1:c.602T>C NP_001395430.1:p.Leu201Ser missense NM_001408502.1:c.533T>C NP_001395431.1:p.Leu178Ser missense NM_001408503.1:c.599T>C NP_001395432.1:p.Leu200Ser missense NM_001408504.1:c.599T>C NP_001395433.1:p.Leu200Ser missense NM_001408505.1:c.599T>C NP_001395434.1:p.Leu200Ser missense NM_001408506.1:c.539T>C NP_001395435.1:p.Leu180Ser missense NM_001408507.1:c.539T>C NP_001395436.1:p.Leu180Ser missense NM_001408508.1:c.530T>C NP_001395437.1:p.Leu177Ser missense NM_001408509.1:c.530T>C NP_001395438.1:p.Leu177Ser missense NM_001408510.1:c.485T>C NP_001395439.1:p.Leu162Ser missense NM_001408511.1:c.482T>C NP_001395440.1:p.Leu161Ser missense NM_001408512.1:c.362T>C NP_001395441.1:p.Leu121Ser missense NM_001408513.1:c.656T>C NP_001395442.1:p.Leu219Ser missense NM_001408514.1:c.656T>C NP_001395443.1:p.Leu219Ser missense NM_007297.4:c.4034T>C NP_009228.2:p.Leu1345Ser missense NM_007298.4:c.866T>C NP_009229.2:p.Leu289Ser missense NM_007299.4:c.866T>C NP_009230.2:p.Leu289Ser missense NM_007300.4:c.4175T>C NP_009231.2:p.Leu1392Ser missense NM_007304.2:c.866T>C NP_009235.2:p.Leu289Ser missense NR_027676.2:n.4352T>C non-coding transcript variant NC_000017.11:g.43090954A>G NC_000017.10:g.41242971A>G NG_005905.2:g.127030T>C LRG_292:g.127030T>C LRG_292t1:c.4175T>C LRG_292p1:p.Leu1392Ser - Protein change
- L1392S, L1345S, L289S, L1096S, L121S, L1265S, L1280S, L1281S, L1303S, L1324S, L1365S, L1366S, L162S, L178S, L201S, L221S, L222S, L242S, L248S, L263S, L1264S, L1322S, L1325S, L1344S, L1350S, L1389S, L161S, L177S, L180S, L200S, L208S, L209S, L241S, L287S, L524S, L1224S, L1304S, L1351S, L1391S, L247S, L249S, L250S, L288S, L1321S, L218S, L219S, L244S, L262S, L286S
- Other names
- -
- Canonical SPDI
- NC_000017.11:43090953:A:G
-
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.
-
The Genome Aggregation Database (gnomAD), exomes 0.00000
Exome Aggregation Consortium (ExAC) 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 |
13044 | 14850 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Aug 3, 2023 | RCV000701502.8 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Sep 16, 2023 | RCV004026559.1 |
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 03, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000830305.4
First in ClinVar: Oct 10, 2018 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 578485). This missense change has been observed in individual(s) with breast cancer (PMID: 29470806). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1392 of the BRCA1 protein (p.Leu1392Ser). (less)
|
|
|
Uncertain significance
(Sep 16, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV005025782.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The p.L1392S variant (also known as c.4175T>C), located in coding exon 10 of the BRCA1 gene, results from a T to C substitution at nucleotide … (more)
The p.L1392S variant (also known as c.4175T>C), located in coding exon 10 of the BRCA1 gene, results from a T to C substitution at nucleotide position 4175. The leucine at codon 1392 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
Comment:
Comment:
The p.L1392S variant (also known as c.4175T>C), located in coding exon 10 of the BRCA1 gene, results from a T to C substitution at nucleotide position 4175. The leucine at codon 1392 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 578485). This missense change has been observed in individual(s) with breast cancer (PMID: 29470806). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1392 of the BRCA1 protein (p.Leu1392Ser).
Comment:
The p.L1392S variant (also known as c.4175T>C), located in coding exon 10 of the BRCA1 gene, results from a T to C substitution at nucleotide position 4175. The leucine at codon 1392 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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 |
|---|---|---|---|---|
| Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations. | Singh J | Breast cancer research and treatment | 2018 | PMID: 29470806 |
Text-mined citations for rs778319854 ...
HelpThese citations are identified by LitVar using
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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.