Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000041364 | SCV000065057 | likely pathogenic | Primary dilated cardiomyopathy | 2012-12-04 | criteria provided, single submitter | clinical testing | The Gln255fs variant in LMNA has not been reported but has been identified in on e individual with reduced ejection fraction (this individual's brother) previous ly tested by our laboratory. This frameshift variant is predicted to alter the p rotein?s amino acid sequence beginning at position 255 and lead to a premature t ermination codon 225 amino acids downstream. This alteration is then predicted t o lead to a truncated or absent protein. Heterozygous loss of function of functi on of the LMNA gene is an established disease mechanism in DCM patients. In summ ary, the Gln255fs variant is likely to be pathogenic. |
| Invitae | RCV003581569 | SCV004292913 | pathogenic | Charcot-Marie-Tooth disease type 2 | 2023-03-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 48079). This premature translational stop signal has been observed in individual(s) with cardiomyopathy (PMID: 24503780, 27532257). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln255Argfs*225) in 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: 18585512, 18926329). |