ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.1838G>A (p.Gly613Asp) (rs148040591)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins NTD, LLC RCV000180334 SCV000232746 uncertain significance not provided 2015-06-03 criteria provided, single submitter clinical testing
Personalized Diabetes Medicine Program,University of Maryland School of Medicine RCV000445510 SCV000536964 likely benign Monogenic diabetes 2018-01-12 criteria provided, single submitter research ACMG criteria: PP3 (2 predictors), BP4 (7 predictors), BP1 (missense in gene with truncating cause disease), Emory calls VUS, cases and controls similar frequency=likely benign
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000825702 SCV000967148 likely benign not specified 2017-08-23 criteria provided, single submitter clinical testing p.Gly612Asp in exon 8 of ALMS1: This variant is not expected to have clinical si gnificance because it has been identified in 0.64% (63/9800) of African chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs148040591).
Invitae RCV001086118 SCV001000876 likely benign Alstrom syndrome 2020-12-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000825702 SCV001482073 likely benign not specified 2021-02-08 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.1835G>A (p.Gly612Asp), also referred to as c.1841G>A (p.Gly614Asp) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00042 in 249178 control chromosomes, predominantly at a frequency of 0.0065 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 3.56 fold of the estimated maximal expected allele frequency for a pathogenic variant in ALMS1 causing Alstrom Syndrome With Dilated Cardiomyopathy phenotype (0.0018), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.1835G>A in individuals affected with Alstrom Syndrome With Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign, n=3; VUS, n=1). Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx RCV000180334 SCV001771979 likely benign not provided 2021-09-02 criteria provided, single submitter clinical testing

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