ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.4028A>T (p.Asp1343Val) (rs775339017)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000467857 SCV000549311 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-10-19 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with valine at codon 1343 of the BRCA1 protein (p.Asp1343Val). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and valine. This variant is present in population databases (rs775339017, ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 409318). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 RCV000510024 SCV000607902 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-18 criteria provided, single submitter clinical testing Insufficient evidence
Integrated Genetics/Laboratory Corporation of America RCV000588993 SCV000699097 uncertain significance not provided 2016-07-11 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.4028A>T (p.Asp1343Val) variant causes a missense change involving a non-conserved nucleotide with 4/4 in silico tools (SNPs&GO not captured due to low reliability index) predicting a damaging outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population with an allele frequency of 1/121376, which does not exceed the estimated maximal expected allele frequency for a pathogenic BRCA1 variant of 1/1000. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Because of the absence of clinical information and the lack of functional studies, the variant has been classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.

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