Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000489372 | SCV000577837 | likely pathogenic | not provided | 2015-04-13 | criteria provided, single submitter | clinical testing | The D168N variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The D168N variant was not observed in approximately 6200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D168N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Additionally, this substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Finally, missense variants in nearby residues (S166F, L167P, R170Q, A171T) have been reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014), supporting the functional importance of this region of the protein.Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded. |
Ambry Genetics | RCV002350090 | SCV002646303 | uncertain significance | Cardiovascular phenotype | 2023-03-28 | criteria provided, single submitter | clinical testing | The p.D168N variant (also known as c.502G>A), located in coding exon 7 of the TNNI3 gene, results from a G to A substitution at nucleotide position 502. The aspartic acid at codon 168 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |