ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1681A>C (p.Ser561Arg)

gnomAD frequency: 0.00001  dbSNP: rs201972250
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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 RCV000823563 SCV000964425 uncertain significance Multiple endocrine neoplasia, type 2 2024-09-25 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 561 of the RET protein (p.Ser561Arg). This variant is present in population databases (rs201972250, gnomAD 0.002%). 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: 665308). 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.
Color Diagnostics, LLC DBA Color Health RCV000823563 SCV004357234 uncertain significance Multiple endocrine neoplasia, type 2 2023-07-27 criteria provided, single submitter clinical testing This missense variant replaces serine with arginine at codon 561 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 been identified in 2/251312 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.
All of Us Research Program, National Institutes of Health RCV000823563 SCV004828606 uncertain significance Multiple endocrine neoplasia, type 2 2023-09-18 criteria provided, single submitter clinical testing This missense variant replaces serine with arginine at codon 561 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 been identified in 2/251312 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.
Ambry Genetics RCV004029146 SCV005028200 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-17 criteria provided, single submitter clinical testing The p.S561R variant (also known as c.1681A>C), located in coding exon 9 of the RET gene, results from an A to C substitution at nucleotide position 1681. The serine at codon 561 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not 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.
Baylor Genetics RCV004569782 SCV005054207 uncertain significance Hirschsprung disease, susceptibility to, 1 2024-01-15 criteria provided, single submitter clinical testing

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