Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001214020 | SCV001385683 | uncertain significance | Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2024-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 7445 of the SYNE1 protein (p.Ile7445Thr). This variant is present in population databases (rs190781696, gnomAD 0.02%). 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: 943759). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
| Revvity Omics, |
RCV003142151 | SCV003824681 | uncertain significance | not provided | 2019-06-24 | criteria provided, single submitter | clinical testing | |
| Pittsburgh Clinical Genomics Laboratory, |
RCV004783918 | SCV005397486 | uncertain significance | Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2023-07-28 | criteria provided, single submitter | clinical testing | This sequence variant is a single nucleotide substitution (T>C) at position 22334 of the coding sequence of the SYNE1 gene that results in an isoleucine to threonine amino acid change at residue 7445 of the SYNE1 protein. This residue falls in spectrin repeat 65 of the SYNE1 protein (UniProt). This is a previously reported variant (ClinVar 943759) that has not been observed in the literature in individuals with SYNE1-related disease, to our knowledge. This variant is present in 8 of 251114 alleles (0.0032%) in the gnomAD population dataset. Multiple bioinformatic tools predict that this isoleucine to threonine amino acid change would be neutral, and the Ile7445 residue at this position is moderately conserved across the vertebrate species examined. Studies examining the functiol consequence of this variant have not been performed, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this a variant of uncertain significance. ACMG Criteria: BP1, BP4, PM2 |