ClinVar Miner

Submissions for variant NM_004387.4(NKX2-5):c.14C>G (p.Pro5Arg)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003090716 SCV003467143 uncertain significance Atrial septal defect 7 2023-12-23 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 5 of the NKX2-5 protein (p.Pro5Arg). 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. ClinVar contains an entry for this variant (Variation ID: 2155617). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NKX2-5 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.
Ambry Genetics RCV003358081 SCV004055665 uncertain significance Cardiovascular phenotype 2023-08-14 criteria provided, single submitter clinical testing The p.P5R variant (also known as c.14C>G), located in coding exon 1 of the NKX2-5 gene, results from a C to G substitution at nucleotide position 14. The proline at codon 5 is replaced by arginine, an amino acid with dissimilar properties. 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.

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