Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000009582 | SCV002246861 | uncertain significance | Atrial septal defect 7 | 2022-03-19 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 9016). This missense change has been observed in individual(s) with NKX2-5-related conditions (PMID: 15810002). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 190 of the NKX2-5 protein (p.Arg190Cys). 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. 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. This variant disrupts the p.Arg190 amino acid residue in NKX2-5. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15364612, 15810002, 20456451). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. |
OMIM | RCV000009582 | SCV000029800 | pathogenic | Atrial septal defect 7 | 2005-05-15 | no assertion criteria provided | literature only |