ClinVar Miner

Submissions for variant NM_015506.3(MMACHC):c.217C>T (p.Arg73Ter) (rs796051995)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671572 SCV000796560 pathogenic Methylmalonic acidemia with homocystinuria 2017-12-28 criteria provided, single submitter clinical testing
GeneDx RCV000186024 SCV000238986 pathogenic not provided 2018-10-26 criteria provided, single submitter clinical testing This variant is denoted c.217 C>T; p.Arg73Stop(R73X). The R73X nonsense mutation has been reported previously in association with cblC deficiency (Lerner-Ellis, et al., 2006). The R73X mutation is predicted to result in nonsense-mediated mRNA decay or in protein truncation. The variant is found in MMACHC panel(s).
Invitae RCV000671572 SCV000959332 pathogenic Methylmalonic acidemia with homocystinuria 2018-08-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg73*) in the MMACHC gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with methylmalonic aciduria and homocystinuria (PMID: 16311595, 27751223, 20631720, Invitae). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 203825). Loss-of-function variants in MMACHC are known to be pathogenic (PMID: 16311595). For these reasons, this variant has been classified as Pathogenic.

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