Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000041353 | SCV000065046 | likely pathogenic | Primary dilated cardiomyopathy | 2014-04-04 | criteria provided, single submitter | clinical testing | The 513+1G>C variant in LMNA has been reported in 1 Taiwanese adult with a clini cal diagnosis and family history of limb girdle muscular dystrophy, cardiac arrh ythmia, and DCM and was absent from 100 control chromosomes (Chen 2013). Data f rom large population studies is insufficient to assess the frequency of this var iant. It has been identified by our laboratory in 1 Caucasian adult with DCM an d muscular dystrophy and 1 affected relative. This variant occurs in the invaria nt region (+/- 1,2) of the splice consensus sequence and is predicted to cause a ltered splicing leading to an abnormal or absent protein. In summary, this varia nt is likely to be pathogenic, though additional studies are required to fully e stablish its clinical significance. |
Invitae | RCV002513582 | SCV003523907 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2022-10-17 | 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: 48069). Disruption of this splice site has been observed in individual(s) with clinical features of LMNA-related conditions (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). |