ClinVar Miner

Submissions for variant NM_020975.6(RET):c.1733T>C (p.Ile578Thr)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002611993 SCV003507702 uncertain significance Multiple endocrine neoplasia, type 2 2022-02-28 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 578 of the RET protein (p.Ile578Thr). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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 RCV003377899 SCV004098452 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-20 criteria provided, single submitter clinical testing The p.I578T variant (also known as c.1733T>C), located in coding exon 9 of the RET gene, results from a T to C substitution at nucleotide position 1733. The isoleucine at codon 578 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly 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.

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