ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2519A>G (p.His840Arg)

dbSNP: rs1588877283
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001015829 SCV001176707 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-16 criteria provided, single submitter clinical testing The p.H840R variant (also known as c.2519A>G), located in coding exon 14 of the RET gene, results from an A to G substitution at nucleotide position 2519. The histidine at codon 840 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is poorly 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.
All of Us Research Program, National Institutes of Health RCV004004550 SCV004823909 uncertain significance Multiple endocrine neoplasia, type 2 2023-02-24 criteria provided, single submitter clinical testing This missense variant replaces histidine with arginine at codon 840 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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