ClinVar Miner

Submissions for variant NM_000071.3(CBS):c.68C>T (p.Ser23Leu)

gnomAD frequency: 0.00001  dbSNP: rs775785018
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002234321 SCV000938069 uncertain significance HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED 2021-09-02 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 23 of the CBS protein (p.Ser23Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs775785018, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with CBS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV001538815 SCV001756518 uncertain significance not provided 2020-06-19 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV003166168 SCV003861112 likely benign Familial thoracic aortic aneurysm and aortic dissection 2023-02-20 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Natera, Inc. RCV000798452 SCV001460092 uncertain significance Classic homocystinuria 2020-01-17 no assertion criteria provided clinical testing

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