ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.94_96del (p.Lys32del) (rs60872029)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000057490 SCV000339264 pathogenic not provided 2016-02-04 criteria provided, single submitter clinical testing
Invitae RCV000459386 SCV000548866 pathogenic Charcot-Marie-Tooth disease, type 2 2019-10-03 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 1 of the LMNA mRNA (c.94_96delAAG). This leads to the deletion of 1 amino acid residue(s) in the LMNA protein (p.Lys32del) but otherwise preserves the integrity of the reading frame. While this variant is not present in population databases (rs60872029), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported in individuals affected with Emery-Dreifuss muscular dystrophy (EDMD), congenital muscular dystrophy, and inflammatory myopathy, (PMID: 12467752, 15372542, 24806962, 27600705, 21632249, 20980393, 26098624, 17377071). This variant has been shown to arise de novo in an individual affected with congenital muscular dystrophy (PMID: 18551513). ClinVar contains an entry for this variant (Variation ID: 66960). Experimental studies of this variant in model organisms have shown that this deletion variant leads to abnormal protein localization, defective filament assembly, and altered protein-protein interactions (PMID: 21653823, 22090424). In addition, homozygous expression of this variant in a mouse model leads to abnormal muscle development, metabolic defects, and shortened survival (PMID: 22090424). Functional characterization of this variant in cultured patient cells has revealed defects in the cellular response to mechanical stress, and altered sub-cellular structural integrity (PMID 24806962, 15372542, 23427149). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000015625 SCV000035890 pathogenic Congenital muscular dystrophy, LMNA-related 2005-08-01 no assertion criteria provided literature only
Epithelial Biology; Institute of Medical Biology, Singapore RCV000057490 SCV000088604 not provided not provided no assertion provided not provided

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