ClinVar Miner

Submissions for variant NM_020975.6(RET):c.161A>G (p.His54Arg)

dbSNP: rs756858300
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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 RCV001906895 SCV002179250 uncertain significance Multiple endocrine neoplasia, type 2 2025-01-05 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 54 of the RET protein (p.His54Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1406391). 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 RCV002388812 SCV002703222 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-05 criteria provided, single submitter clinical testing The p.H54R variant (also known as c.161A>G), located in coding exon 2 of the RET gene, results from an A to G substitution at nucleotide position 161. The histidine at codon 54 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
GeneDx RCV003442949 SCV004170902 uncertain significance not provided 2023-04-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 14633923)
All of Us Research Program, National Institutes of Health RCV001906895 SCV005430274 uncertain significance Multiple endocrine neoplasia, type 2 2024-05-14 criteria provided, single submitter clinical testing This missense variant replaces histidine with arginine at codon 54 of the RET protein. Computational prediction suggests that this variant may not impact protein structure and function. 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 been identified in 1/250912 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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