Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002993899 | SCV003293374 | uncertain significance | Cobalamin C disease | 2022-06-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 89 of the MMACHC protein (p.Arg89His). This variant is present in population databases (rs376520909, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MMACHC-related conditions. 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 not expected to disrupt MMACHC protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV002988767 | SCV003643475 | uncertain significance | Inborn genetic diseases | 2024-02-13 | criteria provided, single submitter | clinical testing | The c.266G>A (p.R89H) alteration is located in exon 2 (coding exon 2) of the MMACHC gene. This alteration results from a G to A substitution at nucleotide position 266, causing the arginine (R) at amino acid position 89 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Genome- |
RCV002993899 | SCV004178143 | uncertain significance | Cobalamin C disease | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002993899 | SCV005653447 | uncertain significance | Cobalamin C disease | 2024-06-15 | criteria provided, single submitter | clinical testing |