ClinVar Miner

Submissions for variant NM_020975.6(RET):c.538C>T (p.Arg180Ter)

dbSNP: rs76449634
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001206325 SCV001377627 pathogenic Multiple endocrine neoplasia, type 2 2019-06-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in RET are known to be pathogenic (PMID: 22174939, 22648184). This variant has been observed in a family affected with Hirschsprung's disease (PMID: 8114939). ClinVar contains an entry for this variant (Variation ID: 13925). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg180*) in the RET gene. It is expected to result in an absent or disrupted protein product.
OMIM RCV000014950 SCV000035206 risk factor Hirschsprung disease, susceptibility to, 1 1994-01-27 no assertion criteria provided literature only
PreventionGenetics, part of Exact Sciences RCV004528111 SCV004112615 pathogenic RET-related disorder 2024-01-02 no assertion criteria provided clinical testing The RET c.538C>T variant is predicted to result in premature protein termination (p.Arg180*). This variant was reported in an individual with Hirschsprung disease (Table 1, Edery et al 1994. PubMed ID: 8114939). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in RET are frequently reported to be pathogenic for Hirschsprung disease (HGMD, Human Gene Mutation Database). We interpret this variant as pathogenic.

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