ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1897C>G (p.Leu633Val)

gnomAD frequency: 0.00003  dbSNP: rs267607010
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000196130 SCV000255047 uncertain significance Multiple endocrine neoplasia, type 2 2023-12-20 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 633 of the RET protein (p.Leu633Val). This variant is present in population databases (rs267607010, gnomAD 0.01%). This missense change has been observed in individual(s) with breast cancer (PMID: 36315513). This missense change has been observed to co-occur in individuals with a different variant in RET that has been determined to be pathogenic (PMID: 8099202), but the significance of this finding is unclear. ClinVar contains an entry for this variant (Variation ID: 216718). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV000410079 SCV000489999 uncertain significance Multiple endocrine neoplasia, type 2b 2016-09-13 criteria provided, single submitter clinical testing
Counsyl RCV000411153 SCV000490000 uncertain significance Multiple endocrine neoplasia, type 2a 2016-09-13 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV002478712 SCV002774861 uncertain significance not provided 2021-08-18 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002503784 SCV002816466 uncertain significance Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia, type 2b; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia, type 2a 2022-04-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV003165476 SCV003911390 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-18 criteria provided, single submitter clinical testing The p.L633V variant (also known as c.1897C>G), located in coding exon 11 of the RET gene, results from a C to G substitution at nucleotide position 1897. The leucine at codon 633 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not 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.
Myriad Genetics, Inc. RCV000411153 SCV004018502 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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