ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.1979C>T (p.Thr660Met) (rs199682595)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481060 SCV000572967 uncertain significance not provided 2017-12-19 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALMS1 gene. The T660M variant has not been published as pathogenic or been reported as benign to our knowledge. It has been observed in several other individuals referred for cardiomyopathy genetic testing at GeneDx, although a second variant in the ALMS1 gene was not identified. The T660M variant is also observed in 22/125830 (0.02%) alleles from individuals of European (non-Finnish) ancestry in large population cohorts (Lek et al., 2016). The T660M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Finally, although some missense variants have been reported in association with Alstrom syndrome, most pathogenic variants in ALMS1 reported to date are predicted to cause premature protein truncation (Marshall et al., 2012; Stenson et al., 2014).
Invitae RCV001070586 SCV001235845 uncertain significance Alstrom syndrome 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 660 of the ALMS1 protein (p.Thr660Met). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs199682595, ExAC 0.02%). This variant has not been reported in the literature in individuals with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 423290). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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.