ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1151C>G (p.Pro384Arg)

gnomAD frequency: 0.00001  dbSNP: rs771679592
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000469726 SCV000543801 uncertain significance Multiple endocrine neoplasia, type 2 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 384 of the RET protein (p.Pro384Arg). This variant is present in population databases (rs771679592, gnomAD 0.003%). 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: 405529). 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.
Ambry Genetics RCV000571320 SCV000674759 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-13 criteria provided, single submitter clinical testing The p.P384R variant (also known as c.1151C>G), located in coding exon 6 of the RET gene, results from a C to G substitution at nucleotide position 1151. The proline at codon 384 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV000679711 SCV000806996 uncertain significance not provided 2017-04-13 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000764895 SCV000896055 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
GeneDx RCV000679711 SCV002513595 uncertain significance not provided 2023-08-17 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; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 14633923)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679711 SCV002774852 uncertain significance not provided 2021-08-11 criteria provided, single submitter clinical testing
Baylor Genetics RCV003463860 SCV004208657 uncertain significance Hirschsprung disease, susceptibility to, 1 2023-10-16 criteria provided, single submitter clinical testing

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