ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.13909G>A (p.Asp4637Asn) (rs142388112)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000263822 SCV000334050 likely benign not specified 2016-09-22 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000357277 SCV000461187 benign Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000260305 SCV000461188 uncertain significance Spinocerebellar ataxia, autosomal recessive 8 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000546895 SCV000649037 uncertain significance Spinocerebellar ataxia, autosomal recessive 8; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2019-05-09 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 4566 of the SYNE1 protein (p.Asp4566Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs142388112, ExAC 0.2%). This variant has not been reported in the literature in individuals with SYNE1-related disease. ClinVar contains an entry for this variant (Variation ID: 282531). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
GeneDx RCV000836067 SCV000977895 likely benign not provided 2018-04-09 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Athena Diagnostics Inc RCV000836067 SCV001145882 likely benign not provided 2018-12-29 criteria provided, single submitter clinical testing

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