ClinVar Miner

Submissions for variant NM_004387.4(NKX2-5):c.169G>C (p.Ala57Pro)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002595959 SCV003499336 uncertain significance Atrial septal defect 7 2022-07-29 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 57 of the NKX2-5 protein (p.Ala57Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NKX2-5-related conditions. 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 proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Revvity Omics, Revvity RCV003130847 SCV003815934 uncertain significance not provided 2022-10-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV003274265 SCV004006445 uncertain significance Cardiovascular phenotype 2023-05-18 criteria provided, single submitter clinical testing The p.A57P variant (also known as c.169G>C), located in coding exon 1 of the NKX2-5 gene, results from a G to C substitution at nucleotide position 169. The alanine at codon 57 is replaced by proline, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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