Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CSER _CC_NCGL, |
RCV000148779 | SCV000190517 | uncertain significance | Aganglionic megacolon | 2014-06-01 | criteria provided, single submitter | research | Low GERP score may suggest that this variant may belong in a lower pathogenicity class |
Invitae | RCV000470554 | SCV000543838 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 475 of the RET protein (p.Arg475Gln). This variant is present in population databases (rs138624658, gnomAD 0.007%). This missense change has been observed in individual(s) with Hirschsprung disease (PMID: 20473317). ClinVar contains an entry for this variant (Variation ID: 135188). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV001011481 | SCV001171807 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-11 | criteria provided, single submitter | clinical testing | The p.R475Q variant (also known as c.1424G>A), located in coding exon 7 of the RET gene, results from a G to A substitution at nucleotide position 1424. The arginine at codon 475 is replaced by glutamine, an amino acid with highly similar properties. This variant has been reported in a patient with sporadic Hirschsprung disease (Attié T et al. Hum. Mol. Genet. 1995 Aug;4:1381-6). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
ITMI | RCV000121995 | SCV000086206 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |