ClinVar Miner

Submissions for variant NM_170707.4(LMNA):c.958del (p.Leu320fs)

dbSNP: rs397517915
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000041381 SCV000065074 pathogenic Primary dilated cardiomyopathy 2013-02-27 criteria provided, single submitter clinical testing The Leu320fs variant in LMNA is predicted to alter the protein?s amino acid sequ ence beginning at position 320 and lead to a premature termination codon 160 ami no acids downstream. This alteration is then predicted to lead to a truncated or absent protein. This variant has been detected in 1 individual tested by our la boratory and was absent from 380 race matched control chromosomes (Lakdawala 201 2). A different variant leading to a nearly identical amino acid change (c.959de lT; Arg321fsX159) has been reported in 5 affected individuals in one family with variable expression of DCM, arrhythmia and muscular dystrophy (Brodsky 2000). C onsidering this second family, the Leu320fs variant meets our criteria to be cla ssified as pathogenic (http://pcpgm.partners.org/LMM).
GeneDx RCV000236709 SCV000293395 pathogenic not provided 2019-11-11 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Many other downstream frameshift variants in the LMNA gene have been reported in HGMD in association with DCM (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 27532257, 24503780, 22464770, 24846508, 31383942, 31402444)
Labcorp Genetics (formerly Invitae), Labcorp RCV001069384 SCV001234548 pathogenic Charcot-Marie-Tooth disease type 2 2019-01-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu320Phefs*160) in the LMNA gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with dilated cardiomyopathy (PMID: 22464770, 27532257). ClinVar contains an entry for this variant (Variation ID: 48095). Loss-of-function variants in LMNA are known to be pathogenic (PMID: 18585512, 18926329). For these reasons, this variant has been classified as Pathogenic.

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