ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.284T>C (p.Ile95Thr) (rs1347662650)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000557426 SCV000649831 uncertain significance Homocystinuria due to CBS deficiency 2017-09-29 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 95 of the CBS protein (p.Ile95Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CBS-related disease. This variant has been observed on opposite chromosomes (in trans) with a CBS pathogenic variant in individuals from a family affected with elevated plasma homocystine levels with evidence of segregation (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with evidence of co-segregation with CBS-related disease.  However, the impact of this variant on protein function is uncertain. It has been classified as a Variant of Uncertain Significance.

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