ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.953C>T (p.Thr318Met) (rs769541394)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755893 SCV000883540 uncertain significance not provided 2018-06-29 criteria provided, single submitter clinical testing The CBS c.953C>T; p.Thr318Met variant (rs769541394), to our knowledge, is not reported in the medical literature in association with a CBS related disorder, but it is reported as a variant of uncertain significance in ClinVar (Variation ID: 405378). This variant is found in the general population with an overall allele frequency of 0.0045% (11/245,976 alleles) in the Genome Aggregation Database. The threonine at codon 318 is weakly conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the c.953C>T variant is uncertain at this time.
Counsyl RCV000468076 SCV000799106 uncertain significance Homocystinuria due to CBS deficiency 2018-04-12 criteria provided, single submitter clinical testing
Invitae RCV000468076 SCV000543520 uncertain significance Homocystinuria due to CBS deficiency 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 318 of the CBS protein (p.Thr318Met). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs769541394, ExAC 0.03%). This variant has not been reported in the literature in individuals with CBS-related disease. ClinVar contains an entry for this variant (Variation ID: 405378). 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: "Deleterious"; PolyPhen-2: "Benign"; 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.

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