ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.493T>G (p.Cys165Gly) (rs1234354755)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000704014 SCV000832947 uncertain significance Homocystinuria due to CBS deficiency 2018-07-26 criteria provided, single submitter clinical testing This sequence change replaces cysteine with glycine at codon 165 of the CBS protein (p.Cys165Gly). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CBS-related disease. 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: "Probably Damaging"; Align-GVGD: "Class C0"). Variants that disrupt the p.Cys165 amino acid residue in CBS have been observed in affected individuals (PMID: 10215408, 7635485). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. 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.

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