ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2531G>T (p.Arg844Leu)

dbSNP: rs55947360
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409297 SCV000490007 uncertain significance Multiple endocrine neoplasia, type 2b 2016-09-20 criteria provided, single submitter clinical testing
Counsyl RCV000410406 SCV000490008 uncertain significance Multiple endocrine neoplasia, type 2a 2016-09-20 criteria provided, single submitter clinical testing
Invitae RCV000460812 SCV000543811 uncertain significance Multiple endocrine neoplasia, type 2 2023-03-15 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 844 of the RET protein (p.Arg844Leu). 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. 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. ClinVar contains an entry for this variant (Variation ID: 24952). This missense change has been observed in individual(s) with medullary thyroid cancer (PMID: 10826520, 28946813). This variant is present in population databases (rs55947360, gnomAD 0.002%).
Ambry Genetics RCV002426514 SCV002740537 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-23 criteria provided, single submitter clinical testing The p.R844L variant (also known as c.2531G>T), located in coding exon 14 of the RET gene, results from a G to T substitution at nucleotide position 2531. The arginine at codon 844 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been reported in individuals with familial medullary thyroid cancer; however, these individuals also carried another RET mutation, p.V804M (Bartsch DK et al. Exp Clin Endocrinol Diabetes 2000 ;108(2):128-32; Lebeault M et al. Thyroid 2017 12;27(12):1511-1522). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Myriad Genetics, Inc. RCV000410406 SCV004018469 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.

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