ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.313C>G (p.Leu105Val) (rs1601375543)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000794312 SCV000933711 uncertain significance Classic homocystinuria 2018-09-11 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 105 of the CBS protein (p.Leu105Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with cystathionine beta-synthase deficiency (PMID: 10338090). This variant is also known as g.3680C>G c.313del4 in the literature. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Child Health and Human Development Program,Research Institute of the McGill University Health Center RCV000794312 SCV001424671 pathogenic Classic homocystinuria no assertion criteria provided clinical testing The c.313C>G (L105V) was identified in a patient of French Canadian origin in compound heterozygote with c.676G>A (A226T). Clinical characteristics included lens dislocation and elevated fasting homocysteine. Patient had no intellectual impairment and responds to treatment with vitamin B6.

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