Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV004589841 | SCV000239231 | uncertain significance | not provided | 2024-03-26 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
| ARUP Laboratories, |
RCV001001049 | SCV001158170 | uncertain significance | Mitochondrial DNA depletion syndrome 9 | 2019-02-15 | criteria provided, single submitter | clinical testing | The SUCLG1 c.481C>T; p.Arg161Cys variant (rs141331864), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 203980). This variant is found in the Ashkenazi Jewish population with an overall allele frequency of 0.20% (21/10364 alleles) in the Genome Aggregation Database. The arginine at codon 161 is moderately conserved, but computational analyses (SIFT: tolerated, PolyPhen-2: damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Arg161Cys variant is uncertain at this time. |
| Illumina Laboratory Services, |
RCV001001049 | SCV001298253 | uncertain significance | Mitochondrial DNA depletion syndrome 9 | 2018-01-12 | 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 |
RCV001001049 | SCV002300326 | uncertain significance | Mitochondrial DNA depletion syndrome 9 | 2022-09-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 161 of the SUCLG1 protein (p.Arg161Cys). This variant is present in population databases (rs141331864, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with SUCLG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 203980). 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 SUCLG1 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. |
| Baylor Genetics | RCV001001049 | SCV003835262 | uncertain significance | Mitochondrial DNA depletion syndrome 9 | 2022-07-12 | criteria provided, single submitter | clinical testing |