ClinVar Miner

Submissions for variant NM_004387.4(NKX2-5):c.566G>C (p.Arg189Pro)

dbSNP: rs786205824
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000171010 SCV000223574 uncertain significance not provided 2023-05-10 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; Reported in association with atrial septal defect in published literature based on ClinVar entry (Kolomenski et al., 2020); This variant is associated with the following publications: (PMID: 32369864)
Labcorp Genetics (formerly Invitae), Labcorp RCV000702426 SCV000831280 uncertain significance Atrial septal defect 7 2020-06-04 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NKX2-5-related disease. ClinVar contains an entry for this variant (Variation ID: 190834). This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 189 of the NKX2-5 protein (p.Arg189Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline.

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