ClinVar Miner

Submissions for variant NM_004387.4(NKX2-5):c.533C>T (p.Thr178Met)

dbSNP: rs104893900
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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 RCV000009568 SCV001214744 pathogenic Atrial septal defect 7 2024-10-27 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 178 of the NKX2-5 protein (p.Thr178Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with NKX2-5-related conditions (PMID: 9651244, 12798584, 15810002). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 9004). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt NKX2-5 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects NKX2-5 function (PMID: 10948187, 21677783, 27013732). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000009568 SCV000029786 pathogenic Atrial septal defect 7 2005-07-15 no assertion criteria provided literature only

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