Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Foundation for Research in Genetics and Endocrinology, |
RCV001838845 | SCV002098372 | uncertain significance | Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2021-07-15 | criteria provided, single submitter | clinical testing | A heterozygous missense variation in exon 128 of the SYNE1 gene that results in the amino acid substitution of Glycine for Glutamic acid at codon 7763 was detected. The observed variant c.23288A>G (p.Glu7763Gly) has not been reported in the 1000 genomes and has a minor allele frequency of 0.0007% in the gnomAD database. The in silico prediction of the variant are possibly damaging by PolyPhen-2 (HumDiv) and damaging by SIFT, LRT and MutationTaster2. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as a variant of uncertain significance. |
| Labcorp Genetics |
RCV002545216 | SCV003449807 | uncertain significance | Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2025-01-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 7692 of the SYNE1 protein (p.Glu7692Gly). This variant is present in population databases (rs765427429, gnomAD 0.006%). 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: 1342176). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |