Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002028782 | SCV002290272 | uncertain significance | Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2022-03-18 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs767563434, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. 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 C15"). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 2018 of the SYNE1 protein (p.Arg2018Cys). 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987955 | SCV004804098 | uncertain significance | not specified | 2024-01-03 | criteria provided, single submitter | clinical testing | Variant summary: SYNE1 c.6052C>T (p.Arg2018Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251294 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.6052C>T has been reported in the literature in at least one individual with autism spectrum disorder (e.g., Tuncay_2022). This report does not provide unequivocal conclusions about association of the variant with SYNE1-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 35190550). One submitter has reported clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |