ClinVar Miner

Submissions for variant NM_004387.4(NKX2-5):c.885C>G (p.Phe295Leu)

gnomAD frequency: 0.00011  dbSNP: rs150581386
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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 RCV001066168 SCV001231169 uncertain significance Atrial septal defect 7 2023-11-25 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 295 of the NKX2-5 protein (p.Phe295Leu). This variant is present in population databases (rs150581386, gnomAD 0.02%). 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: 859947). 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) performed at Invitae indicates that this missense variant is not expected to disrupt NKX2-5 protein function with a negative predictive value of 80%. 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 RCV002374974 SCV002683926 uncertain significance Cardiovascular phenotype 2022-04-18 criteria provided, single submitter clinical testing The p.F295L variant (also known as c.885C>G), located in coding exon 2 of the NKX2-5 gene, results from a C to G substitution at nucleotide position 885. The phenylalanine at codon 295 is replaced by leucine, an amino acid with highly similar 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.
Fulgent Genetics, Fulgent Genetics RCV002482097 SCV002786823 uncertain significance Atrial septal defect 7; Conotruncal heart malformations; Hypothyroidism, congenital, nongoitrous, 5; Tetralogy of Fallot; Ventricular septal defect 3; Hypoplastic left heart syndrome 2 2021-10-12 criteria provided, single submitter clinical testing

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