Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
EGL Genetic Diagnostics, |
RCV000271983 | SCV000344730 | uncertain significance | not provided | 2016-08-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000557154 | SCV000649098 | uncertain significance | Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2018-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 6657 of the SYNE1 protein (p.Arg6657His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs139384691, ExAC 0.04%) but has not been reported in the literature in individuals with a SYNE1-related disease. 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. In summary, this variant is a rare missense change with uncertain impact on protein function. Therefore, it has been classified as a Variant of Uncertain Significance. |