ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2286G>C (p.Glu762Asp)

gnomAD frequency: 0.00001  dbSNP: rs1323183090
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001015065 SCV001175858 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-05 criteria provided, single submitter clinical testing The p.E762D variant (also known as c.2286G>C), located in coding exon 13 of the RET gene, results from a G to C substitution at nucleotide position 2286. The glutamic acid at codon 762 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is well 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001054004 SCV001218295 uncertain significance Multiple endocrine neoplasia, type 2 2024-09-21 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 762 of the RET protein (p.Glu762Asp). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 821031). 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 tolerated. 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.
Fulgent Genetics, Fulgent Genetics RCV002481824 SCV002779937 uncertain significance Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A 2021-07-09 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001054004 SCV004832149 uncertain significance Multiple endocrine neoplasia, type 2 2023-11-30 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with aspartic acid at codon 762 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 been identified in 2/250954 chromosomes 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.

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