Submissions for variant NM_020975.6(RET):c.2388G>T (p.Gln796His)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003361049	SCV004056398	uncertain significance	Hereditary cancer-predisposing syndrome	2023-07-10	criteria provided, single submitter	clinical testing	The p.Q796H variant (also known as c.2388G>T), located in coding exon 13 of the RET gene, results from a G to T substitution at nucleotide position 2388. The glutamine at codon 796 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003533850	SCV004312472	uncertain significance	Multiple endocrine neoplasia, type 2	2023-08-06	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 796 of the RET protein (p.Gln796His). This variant is not present in population databases (gnomAD no frequency). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with RET-related conditions.