ClinVar Miner

Submissions for variant NM_144573.3(NEXN):c.157G>A (p.Glu53Lys) (rs373778361)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000621991 SCV000737234 uncertain significance Cardiovascular phenotype 2020-02-03 criteria provided, single submitter clinical testing The p.E53K variant (also known as c.157G>A), located in coding exon 2 of the NEXN gene, results from a G to A substitution at nucleotide position 157. The glutamic acid at codon 53 is replaced by lysine, an amino acid with similar properties. This variant was reported in a left ventricular non-compaction (LVNC) case; however, clinical details were limited (Miszalski-Jamka K et al. Circ Cardiovasc Genet, 2017 Aug;10:[Epub ahead of print]). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000994027 SCV001147317 uncertain significance not provided 2017-04-01 criteria provided, single submitter clinical testing
Invitae RCV001044221 SCV001208006 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2020-08-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 53 of the NEXN protein (p.Glu53Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs373778361, ExAC 0.02%). This variant has been observed in individual(s) with left ventricular noncompaction (PMID: 28798025). ClinVar contains an entry for this variant (Variation ID: 519153). 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: Probably Damaging; 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000994027 SCV001741238 uncertain significance not provided no assertion criteria provided clinical testing

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