Submissions for variant NM_020975.6(RET):c.2467G>A (p.Gly823Arg)

dbSNP: rs138847998

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000393505	SCV000362352	uncertain significance	Multiple endocrine neoplasia	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000307731	SCV000362353	uncertain significance	Pheochromocytoma	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000362457	SCV000362354	uncertain significance	Hirschsprung Disease, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000272691	SCV000362355	uncertain significance	Renal hypodysplasia/aplasia 1	2016-06-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001015632	SCV001176485	uncertain significance	Hereditary cancer-predisposing syndrome	2023-02-16	criteria provided, single submitter	clinical testing	The p.G823R variant (also known as c.2467G>A), located in coding exon 14 of the RET gene, results from a G to A substitution at nucleotide position 2467. The glycine at codon 823 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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.
Invitae	RCV002520586	SCV003273432	uncertain significance	Multiple endocrine neoplasia, type 2	2023-11-02	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 823 of the RET protein (p.Gly823Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 299898). 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. 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.