ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.11953A>G (p.Ile3985Val) (rs201728850)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000705168 SCV000834153 uncertain significance Alstrom syndrome 2019-12-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 3986 of the ALMS1 protein (p.Ile3986Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs201728850, ExAC 0.2%). This variant has not been reported in the literature in individuals with ALMS1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000705168 SCV000897049 uncertain significance Alstrom syndrome 2018-10-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV001195324 SCV001365667 likely benign not specified 2019-10-04 criteria provided, single submitter clinical testing The p.Ile3986Val variant in ALMS1 is classified as likely benign because it has been identified in 0.1% (59/35436) of Latino chromosomes by gnomAD (, and computational prediction tools predict that this variant does not impact the protein. ACMG/AMP Criteria applied: BS1_Supporting, BP4.
Nilou-Genome Lab RCV000705168 SCV001652731 likely benign Alstrom syndrome 2021-05-18 criteria provided, single submitter clinical testing
GeneDx RCV001560085 SCV001782424 uncertain significance not provided 2021-05-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV000705168 SCV001459608 likely benign Alstrom syndrome 2020-04-23 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.