ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.904_905CT[2] (p.Ser303fs) (rs59684335)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000057484 SCV000234727 pathogenic not provided 2017-01-13 criteria provided, single submitter clinical testing The c.908_909delCT pathogenic variant in the LMNA gene has been reported multiple times in association with various features in the laminopathy clinical spectrum (Macleod et al., 2003; Antoniades et al., 2007; Sparks et al., 2011). Macleod et al. initially identified the c.908_909delCT variant in a 45 year old female with features of DCM, conduction disease, family history of sudden death and this variant was absent from 100 control chromosomes. Antoniades et al. reported c.908_909delCT in a family with cardiac conduction disease, DCM, limb-girdle muscular dystrophy, and family history of sudden occurring at early ages. Sparks et al. also reported c.908_909delCT co-segregated with a laminopathy phenotype in one large family with multiple relatives who had sinus bradycardia, atrioventricular arrhythmias, including atrial fibrillation, heart failure, and cardiac sudden death. Moreover, this pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Lastly, other frameshift mutations in the LMNA gene have been reported in HGMD in association with cardiomyopathy/laminopathy (Stenson P et al., 2009). Therefore, the presence of the c.908_909delCT pathogenic variant in the LMNA gene is consistent with a diagnosis of cardiomyopathy/laminopathy.
Invitae RCV000463447 SCV000548852 pathogenic Charcot-Marie-Tooth disease, type 2 2018-11-26 criteria provided, single submitter clinical testing This sequence change deletes 2 nucleotides in exon 5 of the LMNA mRNA (c.908_909delCT), causing a frameshift at codon 303. This creates a premature translational stop signal (p.Ser303Cysfs*27) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in LMNA are known to be pathogenic. This particular variant has been reported to segregate with disease in two families. Affected individuals presented with a range of phenotypes including atrioventricular block, arrhythmia, dilated cardiomyopathy and limb girdle muscular dystrophy (PMID: 17605093, 21691096). ClinVar contains an entry for this variant (Variation ID: 66955). For these reasons, this variant has been classified as Pathogenic.
Genetic Services Laboratory,University of Chicago RCV000502542 SCV000595643 pathogenic Dilated cardiomyopathy 1A 2013-02-08 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000057484 SCV000704598 pathogenic not provided 2017-01-04 criteria provided, single submitter clinical testing
Epithelial Biology; Institute of Medical Biology, Singapore RCV000057484 SCV000088598 not provided not provided no assertion provided not provided
Erich and Hanna Klessmann Institute for Cardiovascular Research and Development,Heart and Diabetes Center North Rhine-Westphalia RCV000490978 SCV000298130 pathogenic Dilated cardiomyopathy 1S 2016-05-01 no assertion criteria provided clinical testing

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