ClinVar Miner

Submissions for variant NM_000071.3(CBS):c.493T>G (p.Cys165Gly)

dbSNP: rs1234354755
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002233403 SCV000832947 pathogenic HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED 2023-08-05 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CBS protein function. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys165 amino acid residue in CBS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7635485, 10215408). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 580466). This missense change has been observed in individual(s) with clinical features of homocystinuria due to CBS deficiency (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 165 of the CBS protein (p.Cys165Gly).
Natera, Inc. RCV000704014 SCV002083808 uncertain significance Classic homocystinuria 2021-06-26 no assertion criteria provided clinical testing

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