Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000185010 | SCV000237797 | uncertain significance | not provided | 2017-05-02 | criteria provided, single submitter | clinical testing | The A637V variant of uncertain significance in the LDB3 gene has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. It has been reported as a variant of uncertain significance by another clinical laboratory in ClinVar (SCV000062424.2; Landrum et al., 2016). The A637V variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. This variant occurs at a position that is highly conserved across species; however, it is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Consequently, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. |
| Ambry Genetics | RCV002362964 | SCV002661620 | uncertain significance | Cardiovascular phenotype | 2020-03-26 | criteria provided, single submitter | clinical testing | The p.Y22544C variant (also known as c.67631A>G), located in coding exon 168 of the TTN gene, results from an A to G substitution at nucleotide position 67631. The tyrosine at codon 22544 is replaced by cysteine, an amino acid with highly dissimilar 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. |