Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV001089963 | SCV001244994 | likely pathogenic | Hirschsprung disease, susceptibility to, 1 | 2018-08-24 | criteria provided, single submitter | clinical testing | A heterozygous missense variant, NM_020975.5(RET):c.2629G>C, has been identified in exon 15 of 20 of the RET gene. The variant is predicted to result in a minor amino acid change from alanine to proline at position 877 of the protein (NP_066124.1(RET):p.(Ala877Pro)). The alanine residue at this position has very high conservation (100 vertebrates, UCSC), and is located within the Proteain kinase functional domain. In silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is absent in population databases (gnomAD, dbSNP). This variant has not been previously reported in clinical cases. Analysis of parental samples indicated this variant to be de novo. Based on the information available at the time of curation, this variant has been classified as LIKELY PATHOGENIC. |