ClinVar Miner

Submissions for variant NM_015506.3(MMACHC):c.567dup (p.Ile190fs) (rs1463495909)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672749 SCV000797885 pathogenic Methylmalonic acidemia with homocystinuria 2018-02-14 criteria provided, single submitter clinical testing
Invitae RCV000672749 SCV000955269 pathogenic Methylmalonic acidemia with homocystinuria 2018-12-22 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MMACHC gene (p.Ile190Tyrfs*13). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 83 amino acids of the MMACHC protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals with clinical features of combined methylmalonic aciduria and homocystinuria(PMID: 21835369, 26149271, 27383490). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 556708). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant disrupts the C-terminus of the MMACHC protein. Another variant that disrupts this region (p.Trp203*) has been determined to be pathogenic (PMID: 16311595, 28327205, 27383490, 20631720, 23954310). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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