Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000265621 | SCV000414298 | uncertain significance | Progressive familial heart block type IB | 2018-01-12 | 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, this variant 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, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Gene |
RCV000616586 | SCV000715317 | likely benign | not specified | 2017-08-21 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
| Labcorp Genetics |
RCV000265621 | SCV001616902 | likely benign | Progressive familial heart block type IB | 2025-01-17 | criteria provided, single submitter | clinical testing | |
| Clinical Genomics Laboratory, |
RCV000265621 | SCV004812186 | uncertain significance | Progressive familial heart block type IB | 2021-06-16 | criteria provided, single submitter | clinical testing | The c.2133-9C>G variant in the TRPM4 gene has not been previously reported in association with disease. This variant has been identified in 15/10,364 Ashkenazi Jewish chromosomes (25/282,680 chromosomes overall) by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Although this variant has been seen in the general population, it has not been observed at a high enough frequency to rule out pathogenicity. The c.2133-9C>G variant occurs in the 3’ splice site and computational tools do not predict an impact to splicing. However, the accuracy of these computational tools is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the c.2133-9C>G variant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: None] |