ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.4405C>A (p.Pro1469Thr) (rs373638043)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Personalized Diabetes Medicine Program,University of Maryland School of Medicine RCV000445538 SCV000536970 uncertain significance Monogenic diabetes 2015-08-07 criteria provided, single submitter research ACMG Criteria: PP3, BP4
Counsyl RCV000666784 SCV000791138 uncertain significance Alstrom syndrome 2017-05-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001201200 SCV001372275 uncertain significance not specified 2020-06-29 criteria provided, single submitter clinical testing Variant summary: ALMS1 c.4402C>A (p.Pro1468Thr, also known as c.4408C>A, p.P1470T) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 249216 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in ALMS1 causing Cardiomyopathy (4.4e-05 vs 0.0022), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.4402C>A in individuals affected with 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 laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
GeneDx RCV001575003 SCV001801911 uncertain significance not provided 2021-05-10 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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