Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000492943 | SCV000582684 | pathogenic | not provided | 2023-02-08 | 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 (gnomAD); This variant is associated with the following publications: (PMID: 12357336, 30304743, 28139241, 26502900, 17166182, 11058895, 23430838, 23430927, 28915903, 33879512, 12705494) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174875 | SCV001338274 | pathogenic | PMM2-congenital disorder of glycosylation | 2020-02-03 | criteria provided, single submitter | clinical testing | Variant summary: PMM2 c.367C>T (p.Arg123X) 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 allele was found at a frequency of 3.1e-05 in 191838 control chromosomes. c.367C>T has been reported in the literature in individuals affected with Congenital Disorder of Glycosylation Type 1a and has subsequently been cited by other reports (example, Briones_2002, Serrano_2017, Quelhas_2007, Perez_2011). These data indicate that the variant is associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Invitae | RCV001174875 | SCV001376340 | pathogenic | PMM2-congenital disorder of glycosylation | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg123*) in the PMM2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMM2 are known to be pathogenic (PMID: 19862844). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with clinical features of PMM2-congenital disorder of glycosylation (PMID: 11058895, 17166182, 23430927, 28139241). ClinVar contains an entry for this variant (Variation ID: 429981). For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV001174875 | SCV004205257 | pathogenic | PMM2-congenital disorder of glycosylation | 2023-09-19 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001174875 | SCV001457171 | pathogenic | PMM2-congenital disorder of glycosylation | 2020-09-16 | no assertion criteria provided | clinical testing |