ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.16C>T (p.Leu6Phe)

gnomAD frequency: 0.00001  dbSNP: rs1315262605
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000815437 SCV000955890 uncertain significance Hereditary breast ovarian cancer syndrome 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 6 of the BRCA1 protein (p.Leu6Phe). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 658584). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is not expected to disrupt BRCA1 function with a negative predictive value of 95%. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 30209399). 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.
Ambry Genetics RCV002397692 SCV002714136 likely benign Hereditary cancer-predisposing syndrome 2021-05-20 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Baylor Genetics RCV001077646 SCV004212683 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2023-10-24 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV002397692 SCV004361142 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-29 criteria provided, single submitter clinical testing This missense variant replaces leucine with phenylalanine at codon 6 of the BRCA1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). This variant has been reported to be functional in a haploid cell proliferation assay (PMID: 30209399). This variant has been reported in 1 individual affected with breast cancer; an exon 2 deletion in BRCA1 was also detected in this individual, but the deletion could not be confirmed (DOI: 10.5812/ijcm.60392). This variant has been identified in 1/251048 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Brotman Baty Institute, University of Washington RCV001077646 SCV001243604 not provided Breast-ovarian cancer, familial, susceptibility to, 1 no assertion provided in vitro

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