ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.8837A>G (p.His2946Arg)

dbSNP: rs574785830
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000609389 SCV000713770 uncertain significance not specified 2017-12-14 criteria provided, single submitter clinical testing The p.His2945Arg variant in ALMS1 has not been previously reported in individual s with hearing loss, but has been identified in 0.14% (42/30780) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinsti tute.org/; dbSNP rs574785830). Although this variant has been seen in the gener al population, its frequency is not high enough to rule out a pathogenic role. C omputational prediction tools and conservation analysis do not provide strong su pport for or against an impact to the protein. In summary, the clinical signific ance of the p.His2945Arg variant is uncertain. ACMG/AMP Criteria applied: None.
Invitae RCV001050820 SCV001214946 uncertain significance Alstrom syndrome 2022-05-16 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 2947 of the ALMS1 protein (p.His2947Arg). This variant is present in population databases (rs574785830, 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: 506219). 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 RCV001584424 SCV001811428 uncertain significance not provided 2019-10-23 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 506219; Landrum et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Ambry Genetics RCV003160072 SCV003912803 likely benign Cardiovascular phenotype 2023-03-13 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.
Natera, Inc. RCV001050820 SCV001455475 uncertain significance Alstrom syndrome 2019-10-28 no assertion criteria provided clinical testing

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