Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000664890 | SCV000788917 | likely pathogenic | Methylmalonic aciduria, cblA type | 2017-01-03 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000664890 | SCV002229810 | pathogenic | Methylmalonic aciduria, cblA type | 2022-04-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn137Lysfs*5) in the MMAA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MMAA are known to be pathogenic (PMID: 15523652, 15781192). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MMAA-related conditions. ClinVar contains an entry for this variant (Variation ID: 550209). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155263 | SCV003844497 | likely pathogenic | Methylmalonic acidemia | 2023-02-01 | criteria provided, single submitter | clinical testing | Variant summary: MMAA c.411_414delTAAA (p.Asn137LysfsX5) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 248738 control chromosomes (gnomAD). To our knowledge, no occurrence of c.411_414delTAAA in individuals affected with Methylmalonic Acidemia and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic, and one as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV000664890 | SCV004193090 | likely pathogenic | Methylmalonic aciduria, cblA type | 2023-10-12 | criteria provided, single submitter | clinical testing |