ClinVar Miner

Submissions for variant NM_002294.3(LAMP2):c.661G>A (p.Gly221Arg) (rs145169006)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037424 SCV000061081 likely benign not specified 2015-05-26 criteria provided, single submitter clinical testing p.Gly221Arg in LAMP2: This variant is not expected to have clinical significance because it has been identified in 0.2% (84/47999) of European chromosomes, incl uding 30 males, by the Exome Aggregation Consortium (ExAC, http://exac.broadins titute.org/; dbSNP rs145169006).
GeneDx RCV000037424 SCV000207890 likely benign not specified 2017-12-13 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000465775 SCV000560067 likely benign Danon disease 2019-12-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755557 SCV000604090 benign not provided 2017-10-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV000617835 SCV000736900 benign Cardiovascular phenotype 2017-06-15 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000037424 SCV000740589 likely benign not specified 2016-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000718230 SCV000849092 benign History of neurodevelopmental disorder 2017-06-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000853049 SCV000995807 benign Cardiomyopathy 2019-05-14 criteria provided, single submitter clinical testing
Human Genetics Laboratory,State University of Rio de Janeiro RCV001089470 SCV000996528 uncertain significance Intellectual disability 2020-04-07 criteria provided, single submitter research
Mendelics RCV000465775 SCV001142004 likely benign Danon disease 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000465775 SCV001330759 benign Danon disease 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Integrated Genetics/Laboratory Corporation of America RCV000037424 SCV001362570 benign not specified 2019-03-04 criteria provided, single submitter clinical testing Variant summary: LAMP2 c.661G>A (p.Gly221Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0015 in 200310 control chromosomes in the gnomAD database, including 1 homozygote and 95 hemizygotes. The observed variant frequency is approximately 120 fold of the estimated maximal expected allele frequency for a pathogenic variant in LAMP2 causing Cardiomyopathy phenotype (1.3e-05), strongly suggesting that the variant is benign. The variant c.661G>A has been reported in the literature in patients with dilated (DCM) or hypertrophic (HCM) cardiomyopathies, however without evidence for causality (e.g. Mook 2013, Cecconi 2016, Mademont-Soler 2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (2x)/likely benign(4x). Based on the evidence outlined above, the variant was classified as benign.
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000465775 SCV000734734 likely benign Danon disease no assertion criteria provided clinical testing

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