Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000488986 | SCV000577134 | pathogenic | not provided | 2020-05-26 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23026888, 15523652, 26270765, 15308131, 17957493, 17948227, 19375370) |
Invitae | RCV000203329 | SCV000641768 | pathogenic | Methylmalonic aciduria, cblA type | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg22*) 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 present in population databases (rs765799472, gnomAD 0.004%). This premature translational stop signal has been observed in individuals with methylmalonic aciduria (PMID: 15308131, 15523652, 17957493, 23026888, 26270765). ClinVar contains an entry for this variant (Variation ID: 218969). For these reasons, this variant has been classified as Pathogenic. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590153 | SCV000699976 | pathogenic | Methylmalonic acidemia | 2017-06-19 | criteria provided, single submitter | clinical testing | Variant summary: The MMAA c.64C>T (p.Arg22X) variant results in a premature termination codon, predicted to cause a truncated or absent MMAA 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 and other laboratories in ClinVar (e.g. p.Arg145X, p.Gln248X, p.Arg330X, etc.). This variant was found in 5/215496 control chromosomes at a frequency of 0.0000232, which does not exceed the estimated maximal expected allele frequency of a pathogenic MMAA variant (0.0018257). This variant has been reported in at least seven unrelated patients with methylmalonic acidemia in homozygous state as well in compound heterozygous state with other pathogenic/likely pathogenic variants (Yang_2004, Lerner-Ellis_2004, Merinero_2008, Dempsey-Nunez_2012, Nizon_2013, Manoli_2016). Biochemical analyses of the patient cells were consistent with severe impairment of enzymatic activity by this variant. A clinical diagnostic laboratory and a reputable database (via ClinVar) have classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
Counsyl | RCV000203329 | SCV000790666 | pathogenic | Methylmalonic aciduria, cblA type | 2017-04-04 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000203329 | SCV004193092 | pathogenic | Methylmalonic aciduria, cblA type | 2023-10-06 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000203329 | SCV000258469 | not provided | Methylmalonic aciduria, cblA type | no assertion provided | literature only | ||
Natera, |
RCV000203329 | SCV001452004 | pathogenic | Methylmalonic aciduria, cblA type | 2020-09-16 | no assertion criteria provided | clinical testing |