Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001972162 | SCV002207988 | uncertain significance | Loeys-Dietz syndrome 2 | 2021-04-17 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs767247716, ExAC 0.01%). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TMPO-related conditions. This sequence change replaces isoleucine with asparagine at codon 222 of the TMPO protein (p.Ile222Asn). The isoleucine residue is weakly conserved and there is a large physicochemical difference between isoleucine and asparagine. |
Ambry Genetics | RCV004042900 | SCV005020323 | uncertain significance | not specified | 2024-01-29 | criteria provided, single submitter | clinical testing | The p.I222N variant (also known as c.665T>A), located in coding exon 4 of the TMPO gene, results from a T to A substitution at nucleotide position 665. The isoleucine at codon 222 is replaced by asparagine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |