ClinVar Miner

Submissions for variant NM_020975.6(RET):c.445TTC[1] (p.Phe150del)

dbSNP: rs776989694
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001315295 SCV001505864 uncertain significance Multiple endocrine neoplasia, type 2 2024-01-24 criteria provided, single submitter clinical testing This variant, c.448_450del, results in the deletion of 1 amino acid(s) of the RET protein (p.Phe150del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs776989694, gnomAD 0.003%). 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: 1016306). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 RCV002329267 SCV002636973 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-11 criteria provided, single submitter clinical testing The c.448_450delTTC variant (also known as p.F150del) is located in coding exon 3 of the RET gene. This variant results from an in-frame TTC deletion at nucleotide positions 448 to 450. This results in the in-frame deletion of a phenylalanine at codon 150. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002476466 SCV002779656 uncertain significance Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A 2022-05-16 criteria provided, single submitter clinical testing
GeneDx RCV004590321 SCV005081445 uncertain significance not provided 2024-05-03 criteria provided, single submitter clinical testing In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Observed in an individual with Hirschsprung disease and exocrine pancreatic insufficiency (PMID: EelenJ2020[article]); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 14633923, EelenJ2020[article])

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