ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2060A>G (p.Tyr687Cys)

gnomAD frequency: 0.00003  dbSNP: rs778793244
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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 RCV001014276 SCV001174968 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-31 criteria provided, single submitter clinical testing The p.Y687C variant (also known as c.2060A>G), located in coding exon 11 of the RET gene, results from an A to G substitution at nucleotide position 2060. The tyrosine at codon 687 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001873254 SCV002310484 uncertain significance Multiple endocrine neoplasia, type 2 2023-10-06 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 687 of the RET protein (p.Tyr687Cys). This variant is present in population databases (rs778793244, gnomAD 0.008%). 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: 820626). 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.
All of Us Research Program, National Institutes of Health RCV001873254 SCV004838647 uncertain significance Multiple endocrine neoplasia, type 2 2023-11-28 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with cysteine at codon 687 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 been identified in 5/281370 chromosomes 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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