Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000779265 | SCV000915840 | uncertain significance | Progressive familial heart block type IB | 2018-12-15 | criteria provided, single submitter | clinical testing | This variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. It was observed by ICSL 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 for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene and cDNA change. No publications were found based on this search. Due to the potential impact of splice donor variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for this disease. |
| Ambry Genetics | RCV002458392 | SCV002739728 | uncertain significance | Cardiovascular phenotype | 2020-08-03 | criteria provided, single submitter | clinical testing | The c.2645+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 17 of the TRPM4 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. However, loss of function of TRPM4 has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002501013 | SCV002812873 | uncertain significance | Progressive familial heart block type IB; Erythrokeratodermia variabilis et progressiva 6 | 2021-09-13 | criteria provided, single submitter | clinical testing |