ClinVar Miner

Submissions for variant NM_020975.6(RET):c.3179A>G (p.Lys1060Arg)

gnomAD frequency: 0.00001  dbSNP: rs370756353
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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 RCV001871332 SCV002150817 uncertain significance Multiple endocrine neoplasia, type 2 2023-12-31 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 1060 of the RET protein (p.Lys1060Arg). This variant is not present in population databases (gnomAD 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: 1385324). 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 tolerated. 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 RCV002324280 SCV002609285 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-04 criteria provided, single submitter clinical testing The p.K1060R variant (also known as c.3179A>G), located in coding exon 19 of the RET gene, results from an A to G substitution at nucleotide position 3179. The lysine at codon 1060 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly 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.
Fulgent Genetics, Fulgent Genetics RCV002503483 SCV002783337 uncertain significance Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A 2022-02-11 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001871332 SCV004838726 uncertain significance Multiple endocrine neoplasia, type 2 2023-10-06 criteria provided, single submitter clinical testing This missense variant replaces lysine with arginine at codon 1060 of the RET protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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