Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000057305 | SCV000331584 | pathogenic | not provided | 2016-02-16 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003298103 | SCV003997345 | uncertain significance | Cardiovascular phenotype | 2023-04-24 | criteria provided, single submitter | clinical testing | The c.1488+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 8 of the LMNA gene. This variant has been detected in an an individual reported to have limb girdle muscular dystrophy, partial epilepsy, and severe dilated cardiomyopathy (Tsao CY et al. J Child Neurol, 2009 Mar;24:346-8). This variant has also been detected in an individual with features of Emery-Dreifuss muscular dystrophy who required a pacemaker (Scharner J et al. Hum Mutat, 2011 Feb;32:152-67). This variant has also been detected in a cohort of patients with neuromuscular conditions; however, details were limited (Ben Yaou R et al. Brain Commun, 2021 Jul;3:fcab075). Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNAdecay; however, direct evidence is unavailable. The exact functional effect of the altered amino acid sequence is unknown. This nucleotide position is highly conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003581574 | SCV004292923 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2024-04-29 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 8 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with clinical features of autosomal dominant muscular dystrophy (PMID: 19258295, 20848652, 34240052; Invitae). ClinVar contains an entry for this variant (Variation ID: 66831). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Epithelial Biology; Institute of Medical Biology, |
RCV000057305 | SCV000088418 | not provided | not provided | no assertion provided | not provided |