ClinVar Miner

Submissions for variant NM_144573.3(NEXN):c.392A>C (p.Gln131Pro) (rs397517858)

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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 RCV000245242 SCV000320624 uncertain significance Cardiovascular phenotype 2015-12-04 criteria provided, single submitter clinical testing The p.Q131P variant (also known as c.392A>C), located in coding exon 4 of the NEXN gene, results from an A to C substitution at nucleotide position 392. The glutamine at codon 131 is replaced by proline, an amino acid with some similar properties. Another alteration affecting the same amino acid, p.Q131E (c.391C>G), has been reported in association with hypertrophic cardiomyopathy(Wang H, Am. J. Hum. Genet. 2010 Nov; 87(5):687-93). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6020 samples (12040 alleles) with coverage at this position. 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 variant remains unclear.
Invitae RCV000817176 SCV000957722 uncertain significance Dilated cardiomyopathy 1CC; Familial hypertrophic cardiomyopathy 20 2018-10-23 criteria provided, single submitter clinical testing This sequence change replaces glutamine with proline at codon 131 of the NEXN protein (p.Gln131Pro). The glutamine residue is highly conserved and there is a moderate physicochemical difference between glutamine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NEXN-related disease. ClinVar contains an entry for this variant (Variation ID: 264597). 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: "Possibly 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.

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