Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001059924 | SCV001224579 | pathogenic | Cobalamin C disease | 2023-08-29 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MMACHC protein function. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 854802). This missense change has been observed in individual(s) with methylmalonic aciduria with homocystinuria due to cobalamin C deficiency (PMID: 28693988; Invitae). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 61 of the MMACHC protein (p.Arg61Pro). |
Gene |
RCV002254949 | SCV002526207 | likely pathogenic | not provided | 2022-06-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28693988) |
Fulgent Genetics, |
RCV001059924 | SCV002811031 | likely pathogenic | Cobalamin C disease | 2022-05-28 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001059924 | SCV004178135 | likely pathogenic | Cobalamin C disease | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV001059924 | SCV004193200 | likely pathogenic | Cobalamin C disease | 2023-04-13 | criteria provided, single submitter | clinical testing |