ClinVar Miner

Submissions for variant NM_020975.6(RET):c.2225C>T (p.Thr742Met)

gnomAD frequency: 0.00003  dbSNP: rs773256580
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167451 SCV000218307 likely benign Hereditary cancer-predisposing syndrome 2022-12-13 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Counsyl RCV000409277 SCV000489875 uncertain significance Multiple endocrine neoplasia type 2B 2016-06-21 criteria provided, single submitter clinical testing
Counsyl RCV000409934 SCV000489876 uncertain significance Multiple endocrine neoplasia type 2A 2016-06-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000654567 SCV000776461 uncertain significance Multiple endocrine neoplasia, type 2 2024-12-04 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 742 of the RET protein (p.Thr742Met). This variant is present in population databases (rs773256580, 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: 187701). 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 disruptive. 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.
Fulgent Genetics, Fulgent Genetics RCV000764899 SCV000896059 uncertain significance Congenital central hypoventilation; Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A 2018-10-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV004567352 SCV005054237 uncertain significance Hirschsprung disease, susceptibility to, 1 2023-11-11 criteria provided, single submitter clinical testing
GeneDx RCV004786479 SCV005401617 uncertain significance not provided 2024-05-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in a healthy individual undergoing genetic testing (PMID: 25425582); This variant is associated with the following publications: (PMID: Huret2020[article], 14633923, 25425582)

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