ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.4163C>T (p.Pro1388Leu)

gnomAD frequency: 0.00001  dbSNP: rs377354387
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Total submissions: 5
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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 RCV000445475 SCV000536969 likely benign Monogenic diabetes 2016-07-19 criteria provided, single submitter research ACMG Criteria: PP3, BP1, BP4
Labcorp Genetics (formerly Invitae), Labcorp RCV000537876 SCV000631779 uncertain significance Alstrom syndrome 2022-08-22 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 1389 of the ALMS1 protein (p.Pro1389Leu). This variant is present in population databases (rs377354387, gnomAD 0.01%). 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: 393372). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Not Available"; Align-GVGD: "Not Available". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Counsyl RCV000537876 SCV000791584 uncertain significance Alstrom syndrome 2017-05-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV004022532 SCV005026838 likely benign Cardiovascular phenotype 2023-11-21 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.
Natera, Inc. RCV000537876 SCV001458926 uncertain significance Alstrom syndrome 2020-09-16 no assertion criteria provided clinical testing

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