ClinVar Miner

Submissions for variant NM_000071.3(CBS):c.548C>T (p.Ala183Val)

gnomAD frequency: 0.00001  dbSNP: rs374464810
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002310854 SCV000319220 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-05-07 criteria provided, single submitter clinical testing The p.A183V variant (also known as c.548C>T) is located in coding exon 5 of the CBS gene. This alteration results from a C to T substitution at nucleotide position 548. The alanine at codon 183 is replaced by valine, an amino acid with some similar properties. Based on protein sequence alignment, this amino acid position is conserved in available vertebrate species except for one species of fish. 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 variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV002518997 SCV000649841 uncertain significance HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 183 of the CBS protein (p.Ala183Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). 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: 263808). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Natera, Inc. RCV000541664 SCV002083804 uncertain significance Classic homocystinuria 2020-08-04 no assertion criteria provided clinical testing

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