Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000803217 | SCV000943079 | uncertain significance | Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2022-06-20 | 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 3200 of the SYNE1 protein (p.Glu3200Lys). This variant is present in population databases (rs761121679, gnomAD 0.01%). 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: 648478). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |
Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV003446436 | SCV004171891 | uncertain significance | Emery-Dreifuss muscular dystrophy 4, autosomal dominant | criteria provided, single submitter | clinical testing | The missense c.9577G>A(p.Glu3193Lys) variant in SYNE1 gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The p.Glu3193Lys variant has been reported with allele frequency of 0.001% in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid change p.Glu3193Lys in SYNE1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Glu at position 3193 is changed to a Lys changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS). |