ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.1057C>T (p.Gln353Ter) (rs267607623)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182362 SCV000234681 pathogenic not provided 2017-08-16 criteria provided, single submitter clinical testing The Q353X pathogenic variant in the LMNA gene has previously been reported in a Japanese malewith a diagnosis of spinal muscular atrophy type 3 and AV block (Iwahara et al., 2015). His familyhistory was remarkable for gait disturbances and AV block in multiple relatives (Iwahara et al., 2015).This variant is predicted to cause loss of normal protein function either due to the production of anabnormal, truncated protein product, or loss of protein from this allele due to nonsense-mediatedmRNA decay. Other downstream nonsense variants in the LMNA gene have been reported in HGMDin association with dilated cardiomyopathy (DCM) or laminopathy (Stenson et al., 2014).Furthermore, the Q353X variant has not been observed in approximately 6,500 individuals ofEuropean and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is nota common, benign variant in these populations.
Invitae RCV000229718 SCV000291542 pathogenic Charcot-Marie-Tooth disease, type 2 2018-09-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 353 (p.Gln353*) of the LMNA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LMNA are known to be pathogenic (PMID: 23183350). This particular variant has been reported in the literature in an individual affected with an LMNA-related disorder (PMID: 25886484). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000247014 SCV000319073 pathogenic Cardiovascular phenotype 2018-04-11 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Rarity in general population databases (dbsnp, esp, 1000 genomes)
Inherited Neuropathy Consortium RCV000790003 SCV000929392 uncertain significance Autosomal dominant distal hereditary motor neuropathy no assertion criteria provided literature only

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