ClinVar Miner

Submissions for variant NM_020975.6(RET):c.488G>A (p.Arg163Gln)

gnomAD frequency: 0.00002  dbSNP: rs149403911
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000795345 SCV000934801 uncertain significance Multiple endocrine neoplasia, type 2 2024-08-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 163 of the RET protein (p.Arg163Gln). This variant is present in population databases (rs149403911, gnomAD 0.01%). 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: 135184). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV002336267 SCV002635694 benign Hereditary cancer-predisposing syndrome 2021-09-02 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV002483230 SCV002775154 uncertain significance Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A 2021-12-14 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000795345 SCV005430292 uncertain significance Multiple endocrine neoplasia, type 2 2024-05-30 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 163 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 hereditary cancer in the literature. This variant has been identified in 5/251418 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.
ITMI RCV000121989 SCV000086200 not provided not specified 2013-09-19 no assertion provided reference population

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