ClinVar Miner

Submissions for variant NM_000071.3(CBS):c.616G>A (p.Val206Met)

gnomAD frequency: 0.00003  dbSNP: rs369220569
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000200147 SCV000249687 uncertain significance not provided 2016-03-07 criteria provided, single submitter clinical testing The V206M variant of uncertain significance in the CBS gene has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. The V206M variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. Although the V206M variant occurs at a position that is conserved across species, it is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with homocystinuria. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV002517997 SCV000769937 uncertain significance HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 206 of the CBS protein (p.Val206Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs369220569, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with CBS-related conditions. ClinVar contains an entry for this variant (Variation ID: 212849). 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"). 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 RCV003278691 SCV004008115 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-03-31 criteria provided, single submitter clinical testing The p.V206M variant (also known as c.616G>A), located in coding exon 5 of the CBS gene, results from a G to A substitution at nucleotide position 616. The valine at codon 206 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000648123 SCV002083799 uncertain significance Classic homocystinuria 2020-03-16 no assertion criteria provided clinical testing

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