Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000808363 | SCV000948470 | likely benign | Charcot-Marie-Tooth Neuropathy X | 2023-10-09 | criteria provided, single submitter | clinical testing | |
| DASA | RCV001836650 | SCV002097286 | likely pathogenic | Charcot-Marie-Tooth disease X-linked dominant 1 | 2022-02-14 | criteria provided, single submitter | clinical testing | The c.37G>A;p.(Val13Met) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 637129; PMID: 22944031) - PS4_moderate. The variant is located in a mutational hot spot and/or critical and well-established functional domain (Connexin) - PM1. The variant is present at low allele frequencies population databases (rs104894820 - gnomAD 0.0006019%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. Pathogenic missense variant in this residue have been reported (ClinVar ID: 10439 - c.37G>T;p.(Val13Leu); PMID: 27544631 - p.(Val13Glu)) - PM5. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is likely pathogenic. |
| Mendelics | RCV001836650 | SCV002516466 | pathogenic | Charcot-Marie-Tooth disease X-linked dominant 1 | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002352304 | SCV002622256 | uncertain significance | Inborn genetic diseases | 2020-10-29 | criteria provided, single submitter | clinical testing | The p.V13M variant (also known as c.37G>A), located in coding exon 1 of the GJB1 gene, results from a G to A substitution at nucleotide position 37. The valine at codon 13 is replaced by methionine, an amino acid with highly similar properties. This alteration has been detected in a small number of individuals who are described as carrying a diagnosis of Charcot-Marie-Tooth neuropathy (Bone LJ et al. Neurobiol Dis, 1997;4:221-30; Liu L et al. Clin Genet, 2017 Jun;91:881-891; Panosyan FB et al. Neurology, 2017 Aug;89:927-935). Based on data from gnomAD, the A allele has an overall frequency of 0.006% (11/182,766) total alleles studied, with 2 hemizygotes observed. The highest observed frequency was 0.033% (9/27,415) of Latino alleles. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Inherited Neuropathy Consortium | RCV000789172 | SCV000928524 | uncertain significance | Charcot-Marie-Tooth disease | flagged submission | literature only | ||
| Inherited Neuropathy Consortium | RCV001027489 | SCV001190064 | likely benign | not provided | no assertion criteria provided | provider interpretation |