Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000182374 | SCV000234707 | likely pathogenic | not provided | 2018-03-20 | criteria provided, single submitter | clinical testing | The c.367_369delAAG likely pathogenic variant in the LMNA gene has been reported previously in association with cardiomyopathy and laminopathy (Keller et al., 2012; Kajino et al., 2014). Keller et al. reported c.367_369delAAG in a 43-year-old woman with severe arrhythmia and a three generation family history of sudden death, cardiomyopathy, and arrhythmia. This variant was inherited from her affected father and was shown to segregate with disease in an affected sibling (Keller et al., 2012). The c.367_369delAAG variant has also been shown to segregate with disease in one relative tested at GeneDx. Kajino et al. reported an additional individual with the c.367_369delAAG variant who was initially diagnosed with childhood fiber type dysplasia (CTFD). The c.367_369delAAG variant has also been reported as a likely pathogenic variant by an outside laboratory in ClinVar (SCV000264016.1; Landrum et al., 2016). The c.367_369delAAG variant results in an in-frame deletion of a Lysine at position 123 of the LMNA gene and is located in the alpha-helical rod domain. Lastly, this variant is not observed in large population cohorts (Lek et al., 2016). |
| Blueprint Genetics | RCV000208440 | SCV000264016 | likely pathogenic | Primary dilated cardiomyopathy | 2015-08-04 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001852313 | SCV002258258 | likely pathogenic | Charcot-Marie-Tooth disease type 2 | 2022-03-18 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 200947). This variant has been observed in individuals with clinical features of autosomal dominant LMNA-related conditions (PMID: 22019351, 24642510; Invitae; external communication). This variant is not present in population databases (gnomAD no frequency). This variant, c.367_369del, results in the deletion of 1 amino acid(s) of the LMNA protein (p.Lys123del), but otherwise preserves the integrity of the reading frame. |