Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000664762 | SCV000788772 | pathogenic | Cobalamin C disease | 2016-12-15 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000664762 | SCV000919674 | pathogenic | Cobalamin C disease | 2018-10-29 | criteria provided, single submitter | clinical testing | Variant summary: MMACHC c.3G>A (p.Met1Ile) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded protein due to translation initiation at a downstream codon. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 246258 control chromosomes (gnomAD). c.3G>A has been reported in the literature in multiple individuals affected with Cobalamin C Disease (Methylmalonic Aciduria with Homocystinuria)(Lerner-Ellis_2006, Nogueira_2008). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV000664762 | SCV001402079 | pathogenic | Cobalamin C disease | 2023-09-24 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the MMACHC mRNA. The next in-frame methionine is located at codon 58. This variant is present in population databases (rs779893448, gnomAD 0.003%). Disruption of the initiator codon has been observed in individuals with combined methylmalonic aciduria and homocystinuria (PMID: 16311595, 18164228, 19760748). ClinVar contains an entry for this variant (Variation ID: 203823). For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000664762 | SCV004178125 | pathogenic | Cobalamin C disease | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001272216 | SCV001453985 | pathogenic | Methylmalonic acidemia with homocystinuria cblC | 2020-09-16 | no assertion criteria provided | clinical testing |