ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.5462C>T (p.Pro1821Leu) (rs200266868)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227137 SCV000290093 uncertain significance Alstrom syndrome 2020-10-13 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1822 of the ALMS1 protein (p.Pro1822Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs200266868, ExAC 0.09%). This variant has been reported in the heterozygous state in an individual affected with Alstrom syndrome who did not have a second variant identified (PMID: 22876109). ClinVar contains an entry for this variant (Variation ID: 241003). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably damaging; Align-GVGD: Class C0). In summary, this is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
GeneDx RCV000731515 SCV000619195 uncertain significance not provided 2021-09-14 criteria provided, single submitter clinical testing Observed heterozygous with no other ALMS1 variant in a patient with Alstrom syndrome (Pieiro-Gallego T et al., 2012); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 22876109)
Counsyl RCV000227137 SCV000790173 uncertain significance Alstrom syndrome 2017-03-07 criteria provided, single submitter clinical testing
Eurofins NTD, LLC RCV000731515 SCV000859344 uncertain significance not provided 2018-02-02 criteria provided, single submitter clinical testing
Personalized Diabetes Medicine Program,University of Maryland School of Medicine RCV001172523 SCV001335576 likely benign Monogenic diabetes 2017-05-19 criteria provided, single submitter research ACMG criteria: PP3 (4 predictors), BP4 (5 predictors), BP1 (missense when truncating is disease causing)=likely benign

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