ClinVar Miner

Submissions for variant NM_144573.4(NEXN):c.1430T>C (p.Ile477Thr)

gnomAD frequency: 0.00001  dbSNP: rs727504658
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000701167 SCV000829953 uncertain significance Dilated cardiomyopathy 1CC; Hypertrophic cardiomyopathy 20 2022-07-06 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 477 of the NEXN protein (p.Ile477Thr). This variant is present in population databases (rs727504658, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with NEXN-related conditions. ClinVar contains an entry for this variant (Variation ID: 201934). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769824 SCV000901250 uncertain significance Cardiomyopathy 2015-09-25 criteria provided, single submitter clinical testing
Ambry Genetics RCV002390473 SCV002701048 uncertain significance Cardiovascular phenotype 2024-03-04 criteria provided, single submitter clinical testing The p.I477T variant (also known as c.1430T>C), located in coding exon 10 of the NEXN gene, results from a T to C substitution at nucleotide position 1430. The isoleucine at codon 477 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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.

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