Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000713687 | SCV000340522 | uncertain significance | not provided | 2017-11-22 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000713687 | SCV000844314 | uncertain significance | not provided | 2017-12-21 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001157443 | SCV001319012 | uncertain significance | Autosomal recessive ataxia, Beauce type | 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. |
Illumina Laboratory Services, |
RCV001157444 | SCV001319013 | benign | Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Mayo Clinic Laboratories, |
RCV000713687 | SCV001713384 | uncertain significance | not provided | 2019-04-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000713687 | SCV001792462 | uncertain significance | not provided | 2021-05-20 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001824722 | SCV002074377 | uncertain significance | not specified | 2022-01-20 | criteria provided, single submitter | clinical testing | Variant summary: SYNE1 c.7456A>G (p.Lys2486Glu) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 251298 control chromosomes, predominantly at a frequency of 0.00074 within the African or African-American subpopulation in the gnomAD database. This frequency is not higher than expected for a pathogenic variant in SYNE1 causing Emery-Dreifuss Muscular Dystrophy 4, Autosomal Dominant, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.7456A>G in individuals affected with Emery-Dreifuss Muscular Dystrophy 4, Autosomal Dominant and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as benign (n=1) and as a variant with unknown significance (n=4). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Invitae | RCV002519270 | SCV003506794 | uncertain significance | Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2022-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 2486 of the SYNE1 protein (p.Lys2486Glu). This variant is present in population databases (rs188146577, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 286922). 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. |
Revvity Omics, |
RCV000713687 | SCV003826351 | likely benign | not provided | 2024-01-11 | criteria provided, single submitter | clinical testing |