ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.1058C>T (p.Thr353Met) (rs121964972)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000249963 SCV000319360 pathogenic Cardiovascular phenotype 2014-11-21 criteria provided, single submitter clinical testing
Counsyl RCV000169466 SCV000220905 likely pathogenic Homocystinuria due to CBS deficiency 2014-11-21 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078106 SCV000225481 pathogenic not provided 2013-02-11 criteria provided, single submitter clinical testing
GeneDx RCV000078106 SCV000249706 pathogenic not provided 2016-09-12 criteria provided, single submitter clinical testing The T353M pathogenic variant in the CBS gene has been reported previously in association with homocystinuria due to cystathionine beta-synthase deficiency (Dawson et al., 1997). Functional studies have demonstrated that this variant results in reduced enzymatic activity (Mayfield et al., 2012). Given the available evidence, we interpret T353M as a pathogenic variant.
Invitae RCV000169466 SCV000769936 pathogenic Homocystinuria due to CBS deficiency 2018-09-11 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 353 of the CBS protein (p.Thr353Met). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs121964972, ExAC 0.01%). This variant has been reported as homozygous or in combination with another CBS variant in multiple individuals affected with homocystinuria (PMID: 9156316, 23812867, 11774777, 12124992, 16479318, 21520339, 14635102, 16205833). ClinVar contains an entry for this variant (Variation ID: 131). Experimental studies have shown that this missense change reduces CBS enzymatic activity in vitro and causes low growth in a yeast assay (PMID: 9156316, 14635102, 22267502). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000154 SCV000020297 pathogenic Homocystinuria, pyridoxine-nonresponsive 2017-07-18 no assertion criteria provided literature only

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