Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000621430 | SCV000736212 | pathogenic | Cardiovascular phenotype | 2017-01-26 | criteria provided, single submitter | clinical testing | The c.1157+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 6 of the LMNA gene. This alteration was reported in a proband with dilated cardiomyopathy (DCM) and ventricular tachycardia/fibrillation and, in addition, was reported in other affected family members (Pasotti M, J. Am. Coll. Cardiol. 2008 Oct; 52(15):1250-60). This variant was also reported in one individual in a DCM cohort (van Spaendonck-Zwarts KY, Eur. J. Heart Fail. 2013 Jun; 15(6):628-36). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as pathogenic. |
| Invitae | RCV002513736 | SCV003523909 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2023-04-09 | 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: 66781). This variant is also known as IVS6+1G>A. Disruption of this splice site has been observed in individual(s) with clinical features of LMNA-related conditions (PMID: 18926329, 22224630, 28790152). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 6 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). |
| Epithelial Biology; Institute of Medical Biology, |
RCV000057242 | SCV000088355 | not provided | not provided | no assertion provided | not provided |