ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.4524G>T (p.Gln1508His)

gnomAD frequency: 0.00001  dbSNP: rs1378400021
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000518278 SCV000615667 uncertain significance not specified 2017-06-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000546273 SCV000649180 uncertain significance Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2021-08-13 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 1515 of the SYNE1 protein (p.Gln1515His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is not present in population databases (ExAC no frequency). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000518278 SCV005380966 uncertain significance not specified 2024-08-16 criteria provided, single submitter clinical testing Variant summary: SYNE1 c.4545G>T (p.Gln1515His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251384 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.4545G>T in individuals affected with SYNE1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 448602). Based on the evidence outlined above, the variant was classified as uncertain significance.

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