ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.8414G>A (p.Arg2805His) (rs201252809)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000440514 SCV000536368 uncertain significance not specified 2017-01-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALMS1 gene. The R2805H variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 0.1-0.2% of alleles from individuals of European ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R2805H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species and where histidine is the wild type in several species. Finally, in silico analysis suggests that this variant likely does not alter the protein structure/function.
Invitae RCV000468894 SCV000541333 uncertain significance Alstrom syndrome 2019-12-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 2805 of the ALMS1 protein (p.Arg2805His). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs201252809, ExAC 0.08%). This variant has not been reported in the literature in individuals with ALMS1-related disease. ClinVar contains an entry for this variant (Variation ID: 393018). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. ClinVar contains an entry for this variant (Variation ID: 393018).
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514773 SCV000610094 uncertain significance not provided 2017-09-05 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000468894 SCV000897045 uncertain significance Alstrom syndrome 2018-10-31 criteria provided, single submitter clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000514773 SCV000924727 uncertain significance not provided 2016-08-16 no assertion criteria provided provider interpretation

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