ClinVar Miner

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

gnomAD frequency: 0.00225  dbSNP: rs148040591
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) 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, Mass General Brigham 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 2024-01-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000825702 SCV001482073 likely benign not specified 2022-08-08 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 3.6 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. Sevenclinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign, n=6; 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
Genetic Services Laboratory, University of Chicago RCV000825702 SCV002070950 likely benign not specified 2018-08-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV002408782 SCV002716400 benign Cardiovascular phenotype 2021-10-29 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV001086118 SCV003928158 uncertain significance Alstrom syndrome criteria provided, single submitter research Potent mutations in ALMS1 are associated with a rare condition called Alstrom syndrome. It can cause excessive eating, insulin resistance. However, no evidence is found to ascertain the role of rs148040591 in Alstrom syndrome yet.
Natera, Inc. RCV001086118 SCV002080431 benign Alstrom syndrome 2019-10-21 no assertion criteria provided clinical testing

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