Submissions for variant NM_020975.6(RET):c.289C>G (p.Leu97Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003297659	SCV004009438	uncertain significance	Hereditary cancer-predisposing syndrome	2023-03-29	criteria provided, single submitter	clinical testing	The p.L97V variant (also known as c.289C>G), located in coding exon 2 of the RET gene, results from a C to G substitution at nucleotide position 289. The leucine at codon 97 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
All of Us Research Program, National Institutes of Health	RCV004009729	SCV004828598	uncertain significance	Multiple endocrine neoplasia, type 2	2023-09-18	criteria provided, single submitter	clinical testing	This missense variant replaces leucine with valine at codon 97 of the RET protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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.