ClinVar Miner

Submissions for variant NM_020975.6(RET):c.509C>T (p.Thr170Ile)

gnomAD frequency: 0.00004  dbSNP: rs200547906
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410582 SCV000489905 uncertain significance Multiple endocrine neoplasia, type 2b 2016-07-28 criteria provided, single submitter clinical testing
Counsyl RCV000411681 SCV000489906 uncertain significance Multiple endocrine neoplasia, type 2a 2016-07-28 criteria provided, single submitter clinical testing
Invitae RCV000701145 SCV000829929 uncertain significance Multiple endocrine neoplasia, type 2 2023-12-08 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 170 of the RET protein (p.Thr170Ile). This variant is present in population databases (rs200547906, gnomAD 0.004%). 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: 41844). 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 RCV001023532 SCV001185431 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-26 criteria provided, single submitter clinical testing The p.T170I variant (also known as c.509C>T), located in coding exon 3 of the RET gene, results from a C to T substitution at nucleotide position 509. The threonine at codon 170 is replaced by isoleucine, an amino acid with similar properties. This variant was detected as a secondary finding in one out of 572 ClinSeq participants, unselected for personal or family history of cancer, who underwent exome sequencing; however, the clinical information for this particular individual was not provided (Johnston JJ et al. Am J Hum Genet, 2012 Jul;91:97-108). This amino acid position is not well 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.
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000034776 SCV000043469 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.

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