ClinVar Miner

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

gnomAD frequency: 0.00064  dbSNP: rs200266868
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227137 SCV000290093 uncertain significance Alstrom syndrome 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1822 of the ALMS1 protein (p.Pro1822Leu). This variant is present in population databases (rs200266868, gnomAD 0.09%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with Alstrom syndrome (PMID: 22876109). ClinVar contains an entry for this variant (Variation ID: 241003). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
GeneDx RCV000731515 SCV000619195 uncertain significance not provided 2022-11-25 criteria provided, single submitter clinical testing Observed heterozygous with no other ALMS1 variant in a patient with Alstrom syndrome in published literature (Pieiro-Gallego T et al., 2012); Observed in a patient with a diagnosis of blindness in published literature, although additional clinical information was not provided (Dieiro et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22876109, 32483926)
Counsyl RCV000227137 SCV000790173 uncertain significance Alstrom syndrome 2017-03-07 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) 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
Ambry Genetics RCV002347904 SCV002650535 likely benign Cardiovascular phenotype 2021-10-22 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
New York Genome Center RCV000227137 SCV003925090 uncertain significance Alstrom syndrome 2022-04-22 criteria provided, single submitter clinical testing

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