ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.11407C>T (p.Pro3803Ser) (rs189032342)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471192 SCV000554315 likely benign Alstrom syndrome 2020-11-25 criteria provided, single submitter clinical testing
Personalized Diabetes Medicine Program,University of Maryland School of Medicine RCV001172498 SCV001335551 likely benign Monogenic diabetes 2018-12-21 criteria provided, single submitter research ACMG criteria: BP1 + BS1 (0.3% MAF in gnomAD Africans) = likely benign (REVEL 0.161 + PP3/5 predictors + BP4/4 predictors = conflicting evidence, not using)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001260369 SCV001437317 likely benign not specified 2020-09-24 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.11404C>T (p.Pro3802Ser) (also referred to as c.11410C>T, p.Pro3804Ser) results in a non-conservative amino acid change located in the Alstrom syndrome protein 1 domain (IPR028781) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00024 in 248974 control chromosomes, predominantly at a frequency of 0.0033 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1.8 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.11404C>T in individuals affected with Alstrom Syndrome With Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two 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 likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx RCV001573772 SCV001875181 uncertain significance not provided 2021-10-20 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26582918)
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001573772 SCV001800121 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV001573772 SCV001924325 likely benign not provided no assertion criteria provided clinical testing

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