ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2987C>T (p.Pro996Leu)

dbSNP: rs1588880114
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001017799 SCV001178945 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-15 criteria provided, single submitter clinical testing The p.P996L variant (also known as c.2987C>T), located in coding exon 18 of the RET gene, results from a C to T substitution at nucleotide position 2987. The proline at codon 996 is replaced by leucine, an amino acid with similar 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001299872 SCV001488986 uncertain significance Multiple endocrine neoplasia, type 2 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 996 of the RET protein (p.Pro996Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). 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: 822438). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Fulgent Genetics, Fulgent Genetics RCV005036290 SCV005669667 uncertain significance Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A 2024-03-13 criteria provided, single submitter clinical testing

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