ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.1451G>A (p.Gly484Asp) (rs374663067)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001707718 SCV000618425 uncertain significance not provided 2021-09-24 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID# 449942; Landrum et al., 2016)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000523025 SCV000864107 uncertain significance not specified 2017-02-06 criteria provided, single submitter clinical testing Variant summary: The ALMS1 c.1451G>A (p.Gly484Asp alternative name c.1454G>A) variant involves the alteration of a non-conserved nucleotide and is predicted to be benign by 2/4 in silico tools (SNPs&GO not captured due to low reliability index). This variant was found in 14/120270 control chromosomes from ExAC, predominantly observed in the African subpopulation at a frequency of 0.001327 (13/9798). This frequency is slightly lower than the estimated maximal expected allele frequency of a pathogenic ALMS1 variant (0.0022361). No homozygotes have been reported in ExAC. It may be a rare polymorphism in African population, however no other supporting evidences are present at this time. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories, nor evaluated for functional impact by in vivo/vitro studies. One internal sample carrying this variant also carries a pathogenic variant SCN5A c.2440C>T (p.Arg814Trp). Because of the absence of sufficient clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000798208 SCV000937810 uncertain significance Alstrom syndrome 2019-07-24 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 485 of the ALMS1 protein (p.Gly485Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs374663067, ExAC 0.1%). This variant has not been reported in the literature in individuals with ALMS1-related disease. ClinVar contains an entry for this variant (Variation ID: 449942). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The aspartic acid 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.