Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV002472098 | SCV002768505 | uncertain significance | Combined oxidative phosphorylation deficiency 39 | 2019-08-28 | criteria provided, single submitter | clinical testing | A heterozygous missense variant, NM_032380.4(GFM2):c.1758G>C, has been identified in exon 18 of 21 of the GFM2 gene. The variant is predicted to result in a major amino acid change from arginine to serine at position 586 of the protein (NP_115756.2(GFM2):p.(Arg586Ser)). The arginine residue at this position has low conservation (100 vertebrates, UCSC), and is located within the Elongation factor G, domain IV functional domain. In silico predictions of pathogenicity for this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is absent in population databases (gnomAD) and has not been previously reported in clinical cases. Based on the information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS). |