Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000790778 | SCV000700308 | pathogenic | not provided | 2017-05-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000203347 | SCV002154498 | pathogenic | Methylmalonic aciduria, cblB type | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 190 of the MMAB protein (p.Arg190Cys). This variant is present in population databases (rs398124434, gnomAD 0.003%). This missense change has been observed in individuals with clinical features of methylmalonic aciduria cobalamin B type (PMID: 16410054, 24059531, 29039164). ClinVar contains an entry for this variant (Variation ID: 96244). 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) performed at Invitae indicates that this missense variant is expected to disrupt MMAB protein function. Experimental studies have shown that this missense change affects MMAB function (PMID: 19625202, 29197662). This variant disrupts the p.Arg190 amino acid residue in MMAB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16410054, 16439175, 19625202; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV000203347 | SCV002812317 | likely pathogenic | Methylmalonic aciduria, cblB type | 2022-02-17 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000203347 | SCV004193156 | pathogenic | Methylmalonic aciduria, cblB type | 2021-11-20 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000203347 | SCV000258527 | not provided | Methylmalonic aciduria, cblB type | no assertion provided | literature only | ||
Counsyl | RCV000203347 | SCV001132248 | likely pathogenic | Methylmalonic aciduria, cblB type | 2019-01-09 | no assertion criteria provided | clinical testing | |
Baumgartner lab, |
RCV000203347 | SCV001738799 | pathogenic | Methylmalonic aciduria, cblB type | 2021-06-01 | no assertion criteria provided | clinical testing |