ClinVar Miner

Submissions for variant NM_013995.2(LAMP2):c.864+3_864+6del (rs397516751)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000157986 SCV000207921 pathogenic not provided 2016-06-30 criteria provided, single submitter clinical testing c.864+3_6delGAGT: IVS6+3_6delGAGT in intron 6 of the LAMP2 gene (NM_002294.2). Using capital letters to denote exonic sequence and lower case letters to denote intronic sequence, the normal sequence with the bases that are deleted in braces is: TGgt{gagt}aaca.The c.864+3_6delGAGT variant in the LAMP2 gene has been reported in association with Danon disease (Arad M et al., 2005; Bui Y et al., 2008). Arad et al. reported c.864+3_6delGAGT (reported as IVS6+1_4delGTGA due to alternate nomenclature) in two brothers with severe cardiomyopathy, and Bui et al. identified this variant in a 16 year old male with early onset cardiomyopathy and Danon disease. This variant destroys the splice donor site in intron 6 and is predicted to cause abnormal gene splicing. Other splice site variants in the LAMP2 gene have been reported in association with Danon disease. In summary, c.864+3_6delGAGT in the LAMP2 gene is interpreted as a pathogenic variant. The variant is found in DCM,HCM panel(s).
Invitae RCV000037432 SCV000815693 pathogenic Danon disease 2018-04-02 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the LAMP2 gene. It does not directly change the encoded amino acid sequence of the LAMP2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with Danon's disease (PMID: 15673802, 25458169, 18282207, Invitae). This variant is also known as IVS6+1_4delGTGA in the literature. ClinVar contains an entry for this variant (Variation ID: 44442). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000844640 SCV000061089 likely pathogenic Hypertrophic cardiomyopathy 2007-03-26 no assertion criteria provided clinical testing

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