ClinVar Miner

Submissions for variant NM_004387.4(NKX2-5):c.701C>T (p.Ser234Leu)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002364862 SCV002661984 uncertain significance Cardiovascular phenotype 2020-08-03 criteria provided, single submitter clinical testing The p.S234L variant (also known as c.701C>T), located in coding exon 2 of the NKX2-5 gene, results from a C to T substitution at nucleotide position 701. The serine at codon 234 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well 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.
GeneDx RCV002464656 SCV002759185 uncertain significance not provided 2022-06-01 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV003120954 SCV003786736 uncertain significance Atrial septal defect 7 2022-08-18 criteria provided, single submitter clinical testing 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. 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: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 234 of the NKX2-5 protein (p.Ser234Leu).

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