Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003581726 | SCV004292952 | pathogenic | Charcot-Marie-Tooth disease, type I | 2023-04-20 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 637757). This variant is also known as 493-1G>C. Disruption of this splice site has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 9187667, 31919945). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 3 of the MPZ gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MPZ are known to be pathogenic (PMID: 14711881). |
Inherited Neuropathy Consortium | RCV000790056 | SCV000929446 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |