ClinVar Miner

Submissions for variant NM_000166.6(GJB1):c.394_395del (p.Trp132fs)

dbSNP: rs1555937168
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000624800 SCV000742559 pathogenic Inborn genetic diseases 2016-05-18 criteria provided, single submitter clinical testing The c.394_395delTG pathogenic mutation, located in coding exon 1 of the GJB1 gene, results from a deletion of two nucleotides between nucleotide positions 394 and 395, causing a translational frameshift with a predicted alternate stop codon. Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Mendelics RCV000990864 SCV001141914 pathogenic Charcot-Marie-Tooth disease X-linked dominant 1 2019-05-28 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001855312 SCV002236671 pathogenic Charcot-Marie-Tooth Neuropathy X 2021-12-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GJB1 protein in which other variant(s) (p.Ser258Profs*2) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 521808). This variant is also known as del GT in codon 131–132. This premature translational stop signal has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 9888385, 10093067). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp132Valfs*14) in the GJB1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 152 amino acid(s) of the GJB1 protein.
Inherited Neuropathy Consortium RCV000789280 SCV000928633 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Inherited Neuropathy Consortium Ii, University Of Miami RCV000990864 SCV004174663 uncertain significance Charcot-Marie-Tooth disease X-linked dominant 1 2016-01-06 no assertion criteria provided literature only

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