ClinVar Miner

Submissions for variant NM_000465.4(BARD1):c.1862T>C (p.Met621Thr)

dbSNP: rs1574737288
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000816396 SCV000956902 uncertain significance Familial cancer of breast 2022-11-03 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 621 of the BARD1 protein (p.Met621Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 659396). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
GeneDx RCV001824383 SCV002074019 uncertain significance not provided 2022-02-03 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 17550235, 18480049)
Ambry Genetics RCV002406860 SCV002724113 uncertain significance Hereditary cancer-predisposing syndrome 2020-11-09 criteria provided, single submitter clinical testing The p.M621T variant (also known as c.1862T>C), located in coding exon 9 of the BARD1 gene, results from a T to C substitution at nucleotide position 1862. The methionine at codon 621 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV000816396 SCV004217216 uncertain significance Familial cancer of breast 2023-07-25 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004723232 SCV005339967 uncertain significance BARD1-related disorder 2024-08-05 no assertion criteria provided clinical testing The BARD1 c.1862T>C variant is predicted to result in the amino acid substitution p.Met621Thr. To our knowledge, this variant has not been reported in the literature in individuals with BARD1 related disease. This variant has not been reported in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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