Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000057283 | SCV000234699 | pathogenic | not provided | 2014-05-28 | criteria provided, single submitter | clinical testing | c.1380+1 G>A: IVS7+1 G>A in intron 7 of the LMNA gene (NM_170707.2). The c.1380+1 G>A mutation in the LMNA gene has been reported previously in at least 2 patients with DCM, and was not reported in at least 480 healthy control chromosomes (van Tintelen J et al., 2007; Magagnotti C et al., 2012). This mutation destroys the canonical splice donor site in intron 7 and is predicted to cause abnormal gene splicing. Other splice site mutations in the LMNA gene have been reported in association with LMNA-related disorders. In summary, c.1380+1 G>A in the LMNA gene is interpreted as a disease-causing mutation. The variant is found in DCM-CRDM panel(s). |
Invitae | RCV000697969 | SCV000826605 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2023-04-15 | 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: 66817). This variant is also known as IVS7+1G>A. Disruption of this splice site has been observed in individuals with laminopathies (PMID: 18035086, 22326558). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 7 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). |
Ambry Genetics | RCV002381366 | SCV002700971 | pathogenic | Cardiovascular phenotype | 2022-01-27 | criteria provided, single submitter | clinical testing | The c.1380+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 7 of the LMNA gene. This variant has been detected in multiple individual with dilated cardiomyopathy (DCM) and/or cardiac conduction defects, and co-segregation with disease has been reported in some families (van Tintelen JP et al. Am Heart J, 2007 Dec;154:1130-9; Millat G et al. Eur J Med Genet, 2011 Aug;54:e570-5; Jansweijer JA et al. Eur J Heart Fail, 2017 04;19:512-521; Park J et al. Genet Med, 2020 01;22:102-111). This variant has also been reported in an individual with DCM and limb-girdle muscular dystrophy (LGMD) (Magagnotti C et al. Biochim Biophys Acta, 2012 Jun;1822:970-9). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In silico splice site analysis predicts that this alteration will weaken the native splice donor site. 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. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
Epithelial Biology; Institute of Medical Biology, |
RCV000057283 | SCV000088396 | not provided | not provided | no assertion provided | not provided | ||
Genome |
RCV001535753 | SCV001749888 | not provided | Dilated cardiomyopathy 1A; Charcot-Marie-Tooth disease type 2B1; Emery-Dreifuss muscular dystrophy 2, autosomal dominant; Hutchinson-Gilford syndrome; Familial partial lipodystrophy, Dunnigan type; Mandibuloacral dysplasia with type A lipodystrophy; Congenital muscular dystrophy due to LMNA mutation; Emery-Dreifuss muscular dystrophy 3, autosomal recessive | no assertion provided | phenotyping only | Variant interpreted as Pathogenic and reported on 09-29-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |