Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001148122 | SCV001308992 | uncertain significance | Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV002559421 | SCV003522306 | uncertain significance | not provided | 2022-04-09 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 650 of the GFM1 protein (p.Met650Val). This variant is present in population databases (rs147847472, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with GFM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 901932). 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 GFM1 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 | RCV002557175 | SCV003728080 | uncertain significance | Inborn genetic diseases | 2021-03-19 | criteria provided, single submitter | clinical testing | The c.1948A>G (p.M650V) alteration is located in exon 16 (coding exon 16) of the GFM1 gene. This alteration results from a A to G substitution at nucleotide position 1948, causing the methionine (M) at amino acid position 650 to be replaced by a valine (V). The in silico prediction for the p.M650V alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Gene |
RCV002559421 | SCV003923810 | uncertain significance | not provided | 2023-05-04 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |