Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001066479 | SCV001231490 | uncertain significance | Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with phenylalanine at codon 4340 of the SYNE1 protein (p.Val4340Phe). The valine residue is highly conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is present in population databases (rs768553487, ExAC 0.006%). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |