ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2530C>T (p.Arg844Trp)

dbSNP: rs377767424
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000456854 SCV000543825 uncertain significance Multiple endocrine neoplasia, type 2 2023-12-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 844 of the RET protein (p.Arg844Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Hirschsprung’s disease (PMID: 16818057). ClinVar contains an entry for this variant (Variation ID: 24950). An algorithm developed specifically for the RET gene suggests that this missense change is likely to be deleterious (PMID: 21479187). 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.
Counsyl RCV000662786 SCV000785595 uncertain significance Multiple endocrine neoplasia, type 2a 2017-09-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV001015858 SCV001176738 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-14 criteria provided, single submitter clinical testing The p.R844W variant (also known as c.2530C>T), located in coding exon 14 of the RET gene, results from a C to T substitution at nucleotide position 2530. The arginine at codon 844 is replaced by tryptophan, 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.
GeneDx RCV001588822 SCV001815392 uncertain significance not provided 2019-09-06 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Observed in a patient with Hirschprung disease (Kim 2006); This variant is associated with the following publications: (PMID: 16818057, 21479187)
Fulgent Genetics, Fulgent Genetics RCV002482896 SCV002785379 uncertain significance Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia, type 2b; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia, type 2a 2022-05-09 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000662786 SCV004018477 uncertain significance Multiple endocrine neoplasia, type 2a 2023-04-18 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV003460491 SCV004208681 uncertain significance Hirschsprung disease, susceptibility to, 1 2023-09-20 criteria provided, single submitter clinical testing

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