ClinVar Miner

Submissions for variant NM_144573.3(NEXN):c.1771A>G (p.Thr591Ala) (rs369019618)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000619359 SCV000740119 uncertain significance Cardiovascular phenotype 2017-02-02 criteria provided, single submitter clinical testing The p.T591A variant (also known as c.1771A>G), located in coding exon 12 of the NEXN gene, results from an A to G substitution at nucleotide position 1771. The threonine at codon 591 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001220795 SCV001392806 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2020-08-07 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 591 of the NEXN protein (p.Thr591Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs369019618, ExAC 0.01%). This variant has not been reported in the literature in individuals with NEXN-related conditions. ClinVar contains an entry for this variant (Variation ID: 520339). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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