ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1264T>C (p.Tyr422His) (rs764186025)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000510130 SCV000607791 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-05 criteria provided, single submitter clinical testing Insufficient evidence
Invitae RCV000637451 SCV000758910 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-07-23 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with histidine at codon 422 of the BRCA1 protein (p.Tyr422His). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and histidine. This variant is present in population databases (rs764186025, ExAC 0.01%). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 441286). 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 histidine 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.
Color RCV000510130 SCV000906502 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-23 criteria provided, single submitter clinical testing

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