Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000235476 | SCV000293293 | likely pathogenic | not provided | 2021-06-29 | criteria provided, single submitter | clinical testing | No data available from control populations to assess the frequency of this variant; This variant is associated with the following publications: (PMID: 23011429, 22464564, 28768847, 26392352, 31827005, 21504505, 28283593) |
| Invitae | RCV000470682 | SCV000544774 | pathogenic | Charcot-Marie-Tooth Neuropathy X | 2024-01-08 | criteria provided, single submitter | clinical testing | This variant occurs in a non-coding region of the GJB1 gene. It does not change the encoded amino acid sequence of the GJB1 protein. This variant also falls at the last nucleotide of exon 1, which is part of the consensus splice site for this exon. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This variant has been observed in individuals with Charcot-Marie-Tooth disease (PMID: 21504505, 22464564, 26392352, 28283593, 28768847; Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as c.-373G>A. ClinVar contains an entry for this variant (Variation ID: 246014). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). For these reasons, this variant has been classified as Pathogenic. |
| Illumina Laboratory Services, |
RCV001249760 | SCV001423793 | pathogenic | Charcot-Marie-Tooth disease X-linked dominant 1 | 2020-03-11 | criteria provided, single submitter | clinical testing | The GJB1 c.-17G>A variant occurs in the last base of the 5' untranslated region. This variant has been reported in at least four studies, in which it is found in a total of 26 individuals from eight unrelated families with Charcot-Marie-Tooth neuropathy X type 1 disorder (CMT1X) (Murphy et al. 2011; Arthur-Farraj et al. 2012; Antoniadi et al. 2015; Tomaselli et al. 2017). Affected individuals included both heterozygous females and hemizygous males, and this variant was shown to segregate with disease in five families (Murphy et al. 2011; Tomaselli et al. 2017). The c.-17G>A variant is not found in the Genome Aggregation Database despite good sequence coverage, so the variant is presumed to be rare. Based on the collective evidence and application of the ACMG criteria, the c.-17G>A variant is classified as pathogenic for Charcot-Marie-Tooth neuropathy X type 1. |
| Athena Diagnostics Inc | RCV000235476 | SCV001476386 | pathogenic | not provided | 2020-07-28 | criteria provided, single submitter | clinical testing | Not found in the gnomAD genomes dataset, and the data is high quality. Found in at least one patient with expected phenotype for this gene. Splicing predictions are inconclusive. Nucleotide conservation is uninformative. Strong co-segregation with disease, and data includes affected and unaffected individuals from multiple families. |
| MGZ Medical Genetics Center | RCV001249760 | SCV002579665 | pathogenic | Charcot-Marie-Tooth disease X-linked dominant 1 | 2021-12-01 | criteria provided, single submitter | clinical testing |