Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000193829 | SCV000249081 | uncertain significance | not specified | 2015-04-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001853112 | SCV002145919 | uncertain significance | Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant | 2022-03-20 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 212337). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. This variant is present in population databases (rs368490158, gnomAD 0.09%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 4708 of the SYNE1 protein (p.Ala4708Ser). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000193829 | SCV004029764 | uncertain significance | not specified | 2023-07-13 | criteria provided, single submitter | clinical testing | Variant summary: SYNE1 c.14122G>T (p.Ala4708Ser) results in a conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 251432 control chromosomes, predominantly at a frequency of 0.00087 within the East Asian subpopulation in the gnomAD database. To our knowledge, no occurrence of c.14122G>T in individuals affected with Emery-Dreifuss Muscular Dystrophy or other SYNE1-related disorders and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and both classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |