ClinVar Miner

Submissions for variant NM_004387.4(NKX2-5):c.886G>A (p.Gly296Ser)

dbSNP: rs1358735679
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519820 SCV000622007 uncertain significance not provided 2021-10-13 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 453141; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 26582918)
New York Genome Center RCV000519820 SCV001441447 uncertain significance not provided 2019-05-31 criteria provided, single submitter clinical testing The heterozygous p.Gly296Ser missense variant in the NKX2-5 gene causes the substitution of a Gly into a Ser residue at position 296. The variant is absent from the gnomAD database indicating it is a rare allele. The in silico prediction tools show conflicting predictions about its pathogenicity. Based on the current evidence, the p.Gly296Ser variant in theNKX2-5 gene is assessed as variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV002525255 SCV003499069 uncertain significance Atrial septal defect 7 2022-07-15 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 453141). This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 296 of the NKX2-5 protein (p.Gly296Ser).

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