Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000235237 | SCV000292786 | pathogenic | not provided | 2023-07-21 | criteria provided, single submitter | clinical testing | Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Reported in an individual with a personal and family history of slowly progressive proximal muscle weakness in addition to early onset atrial fibrillation and conduction disease (Chen et al., 2013); This variant is associated with the following publications: (PMID: 24503780, 36984439, 23360689) |
| Invitae | RCV001379216 | SCV001576975 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2022-11-08 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: 245721). Disruption of this splice site has been observed in individual(s) with dilated cardiomyopathy and/or limb-girdle muscular dystrophy (PMID: 23360689, 24503780). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 2 of the LMNA 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 LMNA are known to be pathogenic (PMID: 18585512, 18926329). |