ClinVar Miner

Submissions for variant NM_020975.6(RET):c.547G>A (p.Gly183Ser)

gnomAD frequency: 0.00001  dbSNP: rs1060500760
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000465091 SCV000543823 uncertain significance Multiple endocrine neoplasia, type 2 2022-08-28 criteria provided, single submitter clinical testing 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. 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 405544). This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 183 of the RET protein (p.Gly183Ser).
Ambry Genetics RCV000564807 SCV000674821 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-24 criteria provided, single submitter clinical testing The p.G183S variant (also known as c.547G>A), located in coding exon 3 of the RET gene, results from a G to A substitution at nucleotide position 547. The glycine at codon 183 is replaced by serine, an amino acid with 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.
All of Us Research Program, National Institutes of Health RCV000465091 SCV004840203 uncertain significance Multiple endocrine neoplasia, type 2 2023-11-20 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 183 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 RET-related disorders 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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