Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics Inc | RCV000516625 | SCV000615588 | uncertain significance | not specified | 2017-06-06 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000767056 | SCV000620646 | uncertain significance | not provided | 2017-09-08 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SYNE1 gene. The V5879L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V5879Lvariant is observed in 2/10406 (0.02%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the V5879L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV000686323 | SCV000813837 | uncertain significance | Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2018-05-26 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with leucine at codon 5879 of the SYNE1 protein (p.Val5879Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs200589166, ExAC 0.02%). This variant has not been reported in the literature in individuals with SYNE1-related disease. ClinVar contains an entry for this variant (Variation ID: 448564). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Ce |
RCV000767056 | SCV001154924 | uncertain significance | not provided | 2018-12-01 | criteria provided, single submitter | clinical testing |