ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.1612C>G (p.Leu538Val) (rs202111717)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476920 SCV000541360 uncertain significance Alstrom syndrome 2017-11-15 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 538 of the ALMS1 protein (p.Leu538Val). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs202111717, ExAC 0.04%). This variant has not been reported in the literature in individuals with a ALMS1-related disease. ClinVar contains an entry for this variant (Variation ID: 403950). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
GeneDx RCV000732324 SCV000582649 uncertain significance not provided 2018-06-06 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALMS1 gene. The L538V variant has not been published as pathogenic or been reported as benign to our knowledge. This variant was observed in 95/276908 (0.03%) alleles from individuals of multiple ethnic backgrounds in large population cohorts (Lek et al., 2016). The L538V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Finally, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000732324 SCV000860266 uncertain significance not provided 2018-04-04 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000476920 SCV000897041 uncertain significance Alstrom syndrome 2018-10-31 criteria provided, single submitter clinical testing

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.