ClinVar Miner

Submissions for variant NM_002294.3(LAMP2):c.877C>T (p.Arg293Ter) (rs727503118)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000844639 SCV000198519 pathogenic Danon disease; Hypertrophic cardiomyopathy 2015-04-23 criteria provided, single submitter clinical testing The p.Arg293X variant in LAMP2 has been reported in 4 individuals with with clin ical findings consistent with Danon disease and occured de novo in 1 of these in dividuals (Lascone 2008, Katznerg 201, Garcia-Pavia 2011). The variant was abse nt from large population studies. This nonsense variant leads to a premature ter mination codon at position 293, which is predicted to lead to a truncated or abs ent protein. Loss of function of the LAMP2 gene is known to cause Danon disease, an X-lined glycogen storage disease that includes cardiomyopathy (HCM and DCM) and skeletal myopathy (Boucek 2011). In summary, this variant meets our criteria to be classified as pathogenic for Danon disease in an X-linked dominant manner ( based upon predicted impact to the protein, de novo occurrence, and absence from controls.
GeneDx RCV000255646 SCV000321864 pathogenic not provided 2017-01-28 criteria provided, single submitter clinical testing The R293X nonsense variant in the LAMP2 gene has been reported previously in an individual with hypertrophic cardiomyopathy; however, additional information and parental studies were not available (Garcia-Pavia et al., 2011). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, it was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.
Invitae RCV000150911 SCV000636868 pathogenic Danon disease 2020-02-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg293*) in the LAMP2 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 several individuals affected with Danon disease or hypertrophic cardiomyopathy (PMID: 20960602, 21896538, 23168931). ClinVar contains an entry for this variant (Variation ID: 163812). Loss-of-function variants in LAMP2 are known to be pathogenic (PMID: 21415759). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000255646 SCV000707999 pathogenic not provided 2017-05-02 criteria provided, single submitter clinical testing

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