ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2329T>C (p.Tyr777His)

dbSNP: rs397507199
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001015207 SCV001176018 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-07 criteria provided, single submitter clinical testing The p.Y777H variant (also known as c.2329T>C), located in coding exon 9 of the BRCA1 gene, results from a T to C substitution at nucleotide position 2329. The tyrosine at codon 777 is replaced by histidine, an amino acid with similar properties. 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.
Color Diagnostics, LLC DBA Color Health RCV001015207 SCV001353931 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001210224 SCV001381699 uncertain significance Hereditary breast ovarian cancer syndrome 2019-05-16 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA1-related conditions. This sequence change replaces tyrosine with histidine at codon 777 of the BRCA1 protein (p.Tyr777His). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and histidine.
University of Washington Department of Laboratory Medicine, University of Washington RCV001015207 SCV003847753 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).

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