ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2945G>A (p.Arg982His)

gnomAD frequency: 0.00001  dbSNP: rs368550200
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000536923 SCV000658463 uncertain significance Multiple endocrine neoplasia, type 2 2025-01-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 982 of the RET protein (p.Arg982His). This variant is present in population databases (rs368550200, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with medullary thyroid cancer (PMID: 33827484). ClinVar contains an entry for this variant (Variation ID: 477359). 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 RCV000763650 SCV000894530 uncertain significance Congenital central hypoventilation; Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001017621 SCV001178727 likely benign Hereditary cancer-predisposing syndrome 2018-01-25 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
Sema4, Sema4 RCV001017621 SCV002529996 uncertain significance Hereditary cancer-predisposing syndrome 2021-08-10 criteria provided, single submitter curation
GeneDx RCV003156261 SCV003845650 uncertain significance not provided 2022-09-21 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with medullary thyroid cancer (Qi et al., 2021); This variant is associated with the following publications: (PMID: 14633923, 33827484)
All of Us Research Program, National Institutes of Health RCV000536923 SCV004817112 uncertain significance Multiple endocrine neoplasia, type 2 2023-06-27 criteria provided, single submitter clinical testing

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