ClinVar Miner

Submissions for variant NM_020975.6(RET):c.430C>T (p.Arg144Cys)

gnomAD frequency: 0.00001  dbSNP: rs1588863984
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001022265 SCV001183980 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-24 criteria provided, single submitter clinical testing The p.R144C variant (also known as c.430C>T), located in coding exon 3 of the RET gene, results from a C to T substitution at nucleotide position 430. The arginine at codon 144 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration was detected in 1 of 97 Hirschsprung disease patients of Southern Chinese ancestry (Ngo DN et al. J. Pediatr. Surg. 2012 Oct;47:1859-64). This amino acid position is not well 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002549550 SCV003441418 uncertain significance Multiple endocrine neoplasia, type 2 2022-04-24 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 144 of the RET protein (p.Arg144Cys). This missense change has been observed in individual(s) with Hirschsprung disease (PMID: 23084198). ClinVar contains an entry for this variant (Variation ID: 824780). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV005047211 SCV005666868 uncertain significance Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A 2024-05-18 criteria provided, single submitter clinical testing

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