ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1192T>G (p.Ser398Ala)

dbSNP: rs2053980032
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001227078 SCV001399417 uncertain significance Hereditary breast ovarian cancer syndrome 2019-10-28 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with alanine at codon 398 of the BRCA1 protein (p.Ser398Ala). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and alanine. This variant has not been reported in the literature in individuals with BRCA1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003158557 SCV003846116 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Ambry Genetics RCV003158557 SCV005025720 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-12 criteria provided, single submitter clinical testing The p.S398A variant (also known as c.1192T>G), located in coding exon 9 of the BRCA1 gene, results from a T to G substitution at nucleotide position 1192. The serine at codon 398 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear.

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