Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001865913 | SCV002227854 | pathogenic | not provided | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 608 of the GFM1 protein (p.Arg608Gln). This variant is present in population databases (rs541171482, gnomAD 0.006%). This missense change has been observed in individual(s) with Leigh-like syndrome (PMID: 35703069). It has also been observed to segregate with disease in related individuals. This variant is also known as c.1880G>A (p.Arg627Gln). ClinVar contains an entry for this variant (Variation ID: 1119996). 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 GFM1 protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Rare Diseases Genetics and Genomics, |
RCV001449604 | SCV001622810 | pathogenic | Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 | 2021-05-19 | no assertion criteria provided | research | NM_001308164.1:c.409G>A; p.Val137Met and NM_001308164.1:c.1880G>A; p.Arg627Gln were found in compound heterozygous form in four affected siblings including three females and one male. Polyphen-2, SIFT and MutationTaster predicted these variants as "disease causing" or "damaging" or "pathogenic". These variants segregated correctly in the four affected siblings and their unaffected parents were heterozygous (mother = c.409G>A; p.Val137Met; father = c.1880G>A; p.Arg627Gln). |