Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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). |
Gene |
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) |
Invitae | RCV001069384 | SCV001234548 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2019-01-14 | criteria provided, single submitter | clinical testing | Loss-of-function variants in LMNA are known to be pathogenic (PMID: 18585512, 18926329). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individuals affected with dilated cardiomyopathy (PMID: 22464770, 27532257). ClinVar contains an entry for this variant (Variation ID: 48095). This variant is not present in population databases (ExAC no frequency). 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. |