ClinVar Miner

Submissions for variant NM_015506.3(MMACHC):c.420G>A (p.Trp140Ter) (rs796051996)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Inserm U 954, Faculté de Médecine de Nancy RCV000190393 SCV000243927 not provided Methylmalonic acidemia with homocystinuria no assertion provided not provided
Invitae RCV000190393 SCV000818736 pathogenic Methylmalonic acidemia with homocystinuria 2018-06-12 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MMACHC gene (p.Trp140*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 143 amino acids of the MMACHC protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with methylmalonic aciduria and homocystinuria (PMID: 16311595). ClinVar contains an entry for this variant (Variation ID: 203827). A different truncation (p.Trp203*) that lies downstream of this variant has been determined to be pathogenic (PMID: 16311595, 23954310, 25772322). This suggests that deletion of this region of the MMACHC protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

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