Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000531061 | SCV000658428 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 635 of the RET protein (p.Arg635Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with congenital anomalies of the kidney and urinary tract and pheochromocytoma (PMID: 24449676, 28566479). ClinVar contains an entry for this variant (Variation ID: 477333). 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 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 | RCV001013629 | SCV001174238 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-05 | criteria provided, single submitter | clinical testing | The p.R635C variant (also known as c.1903C>T), located in coding exon 11 of the RET gene, results from a C to T substitution at nucleotide position 1903. The arginine at codon 635 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration was reported in a patient with isolated unilateral pheochromocytoma and in a patient with unilateral renal agenesis (Huguet I et al. Endocr Pract, 2014 Apr;20:e65-8; Heidet L et al. J. Am. Soc. Nephrol., 2017 Oct;28:2901-2914). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003459263 | SCV004206695 | uncertain significance | Hirschsprung disease, susceptibility to, 1 | 2023-07-14 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004592607 | SCV005078991 | uncertain significance | not provided | 2024-07-12 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 14633923, 25725622, 24449676, 28566479) |