Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000373130 | SCV000453098 | uncertain significance | Marinesco-Sjögren syndrome | 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. |
| Gene |
RCV000766477 | SCV000573802 | uncertain significance | not provided | 2017-03-03 | criteria provided, single submitter | clinical testing | The E441K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E441K variant is observed in 1/10212 (0.01%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species; however, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with SIL1-related disorders (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
| Athena Diagnostics Inc | RCV000766477 | SCV000615271 | uncertain significance | not provided | 2019-10-15 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV000766477 | SCV002062622 | uncertain significance | not provided | 2021-11-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000373130 | SCV003276120 | uncertain significance | Marinesco-Sjögren syndrome | 2022-08-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 441 of the SIL1 protein (p.Glu441Lys). This variant is present in population databases (rs779649580, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SIL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 351074). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |