ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1777G>A (p.Gly593Arg)

dbSNP: rs878855059
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000233935 SCV000290533 uncertain significance Multiple endocrine neoplasia, type 2 2024-11-10 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 593 of the RET protein (p.Gly593Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 241339). 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.
Counsyl RCV000662885 SCV000785796 uncertain significance Multiple endocrine neoplasia type 2A 2017-12-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV002401902 SCV002711209 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-21 criteria provided, single submitter clinical testing The p.G593R variant (also known as c.1777G>A), located in coding exon 10 of the RET gene, results from a G to A substitution at nucleotide position 1777. The glycine at codon 593 is replaced by arginine, an amino acid with dissimilar properties. 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. RCV000662885 SCV004018061 uncertain significance Multiple endocrine neoplasia type 2A 2023-04-17 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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