ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1567A>C (p.Lys523Gln)

dbSNP: rs766278774
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000533025 SCV000658408 uncertain significance Multiple endocrine neoplasia, type 2 2023-10-11 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 523 of the RET protein (p.Lys523Gln). 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: 477319). 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 disruptive. 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.
Mendelics RCV000709115 SCV000838386 uncertain significance Multiple endocrine neoplasia type 2A 2018-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV001012166 SCV001172589 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-24 criteria provided, single submitter clinical testing The p.K523Q variant (also known as c.1567A>C), located in coding exon 8 of the RET gene, results from an A to C substitution at nucleotide position 1567. The lysine at codon 523 is replaced by glutamine, an amino acid with similar properties. 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.
Baylor Genetics RCV003470791 SCV004208647 uncertain significance Hirschsprung disease, susceptibility to, 1 2023-10-20 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000533025 SCV004836323 uncertain significance Multiple endocrine neoplasia, type 2 2023-12-18 criteria provided, single submitter clinical testing This missense variant replaces lysine with glutamine at codon 523 of the RET protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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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