ClinVar Miner

Submissions for variant NM_020975.6(RET):c.937C>T (p.Arg313Trp)

gnomAD frequency: 0.00001  dbSNP: rs1057521089
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766922 SCV000521036 uncertain significance not provided 2024-09-25 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21995290, 14633923, 33057194, 23372769, 35982159)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000432509 SCV000540176 uncertain significance not specified 2016-06-23 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 1 report in hirschsprung proband
Ambry Genetics RCV000572287 SCV000674825 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-26 criteria provided, single submitter clinical testing The p.R313W variant (also known as c.937C>T), located in coding exon 5 of the RET gene, results from a C to T substitution at nucleotide position 937. The arginine at codon 313 is replaced by tryptophan, an amino acid with dissimilar properties. This variant has been previously reported in Spanish individuals with Hirschsprung disease (Núñez-Torres et al., BMC Med. Genet. 2011 Oct;12:138; Luzón-Toro B et al. PLoS ONE, 2013 Jan;8:e54800). This amino acid position is not 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 RCV001053927 SCV001218213 uncertain significance Multiple endocrine neoplasia, type 2 2024-04-10 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 313 of the RET protein (p.Arg313Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Hirschsprung disease (PMID: 21995290, 23372769). ClinVar contains an entry for this variant (Variation ID: 381593). 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. 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.
All of Us Research Program, National Institutes of Health RCV001053927 SCV004833284 uncertain significance Multiple endocrine neoplasia, type 2 2023-08-15 criteria provided, single submitter clinical testing

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