Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001126067 | SCV001285220 | benign | Palmoplantar keratoderma-esophageal carcinoma syndrome | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
| Ambry Genetics | RCV004032264 | SCV004939899 | uncertain significance | Inborn genetic diseases | 2024-01-03 | criteria provided, single submitter | clinical testing | The c.406C>T (p.R136W) alteration is located in exon 5 (coding exon 3) of the RHBDF2 gene. This alteration results from a C to T substitution at nucleotide position 406, causing the arginine (R) at amino acid position 136 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV005093580 | SCV005829711 | uncertain significance | not provided | 2024-12-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 136 of the RHBDF2 protein (p.Arg136Trp). This variant is present in population databases (rs372953205, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RHBDF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 891027). 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 disruptive. 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. |