Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002435149 | SCV002752627 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-19 | criteria provided, single submitter | clinical testing | The p.V945L variant (also known as c.2833G>T), located in coding exon 17 of the RET gene, results from a G to T substitution at nucleotide position 2833. The valine at codon 945 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
All of Us Research Program, |
RCV004808349 | SCV005430399 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-04-16 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with leucine at codon 945 of the RET protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RET-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |