ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.11939C>T (p.Thr3980Ile)

gnomAD frequency: 0.00032  dbSNP: rs200568988
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485283 SCV000573415 uncertain significance not provided 2022-06-27 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
Invitae RCV001040891 SCV001204482 uncertain significance Alstrom syndrome 2022-09-07 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 3981 of the ALMS1 protein (p.Thr3981Ile). This variant is present in population databases (rs200568988, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 423689). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001264558 SCV001442767 uncertain significance not specified 2020-10-01 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.11936C>T (p.Thr3979Ile) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8.4e-05 in 250394 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in ALMS1 causing Alstrom Syndrome With Dilated Cardiomyopathy (8.4e-05 vs 0.0018), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.11936C>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, both citing the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV002350076 SCV002645609 likely benign Cardiovascular phenotype 2021-10-21 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Fulgent Genetics, Fulgent Genetics RCV001040891 SCV002814950 uncertain significance Alstrom syndrome 2022-05-15 criteria provided, single submitter 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.