Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000186023 | SCV000238985 | uncertain significance | not provided | 2023-03-23 | criteria provided, single submitter | clinical testing | Reported as homozygous in a patient with cobalamin C deficiency who was also homozygous for R111X (Lerner-Ellis et al., 2006); 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: 16311595, 28337550, 19370762, 32439973) |
Invitae | RCV000552129 | SCV000640283 | uncertain significance | Cobalamin C disease | 2022-09-19 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 61 of the MMACHC protein (p.Arg61Trp). This variant is present in population databases (rs200483477, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with cobalamin C deficiency (PMID: 16311595, 19370762). ClinVar contains an entry for this variant (Variation ID: 203824). 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. 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. |
Illumina Laboratory Services, |
RCV001099137 | SCV001255560 | uncertain significance | Disorders of Intracellular Cobalamin Metabolism | 2017-05-22 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Elsea Laboratory, |
RCV000552129 | SCV001424219 | uncertain significance | Cobalamin C disease | 2020-04-01 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000552129 | SCV001805874 | uncertain significance | Cobalamin C disease | 2021-07-14 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000186023 | SCV002062805 | uncertain significance | not provided | 2021-11-01 | criteria provided, single submitter | clinical testing | |
MGZ Medical Genetics Center | RCV000552129 | SCV002581507 | uncertain significance | Cobalamin C disease | 2021-08-20 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000552129 | SCV002790524 | uncertain significance | Cobalamin C disease | 2022-04-22 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002517826 | SCV003634758 | uncertain significance | Inborn genetic diseases | 2022-04-14 | criteria provided, single submitter | clinical testing | The c.181C>T (p.R61W) alteration is located in exon 2 (coding exon 2) of the MMACHC gene. This alteration results from a C to T substitution at nucleotide position 181, causing the arginine (R) at amino acid position 61 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Baylor Genetics | RCV003458351 | SCV004183524 | uncertain significance | Methylmalonic aciduria, type cblc | 2023-11-01 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000186023 | SCV004227832 | uncertain significance | not provided | 2023-06-09 | criteria provided, single submitter | clinical testing | |
Genome |
RCV000552129 | SCV000986768 | not provided | Cobalamin C disease | no assertion provided | phenotyping only | Variant interpretted as Uncertain significance and reported on 12/09/2017 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. | |
Natera, |
RCV001277240 | SCV001464147 | uncertain significance | Methylmalonic acidemia with homocystinuria cblC | 2019-08-02 | no assertion criteria provided | clinical testing |