ClinVar Miner

Submissions for variant NM_144573.3(NEXN):c.680T>C (p.Leu227Ser) (rs756273801)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498618 SCV000589585 uncertain significance not provided 2017-06-08 criteria provided, single submitter clinical testing The L227S variant in the NEXN gene has been reported previously as homozygous in an individual with secundum atrial septal defect without cardiomyopathy (Yang et al., 2014). The L227S variant is observed in 1/8618 (0.01%) alleles from individuals of East Asian background in the ExAC dataset (Lek et al., 2016). The L227S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. We interpret L227S as a variant of uncertain significance.
Invitae RCV001059582 SCV001224209 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2019-01-14 criteria provided, single submitter clinical testing This sequence change replaces leucine with serine at codon 227 of the NEXN protein (p.Leu227Ser). The leucine residue is moderately conserved and there is a large physicochemical difference between leucine and serine. This variant is present in population databases (rs756273801, ExAC 0.01%). This variant has been observed in an individual affected with a secundum atrial septal defect (PMID: 24866383). ClinVar contains an entry for this variant (Variation ID: 431969). This variant has been reported to affect NEXN protein function (PMID: 24866383). 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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