ClinVar Miner

Submissions for variant NM_015120.4(ALMS1):c.1870T>C (p.Ser624Pro) (rs767987501)

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
Genetic Services Laboratory, University of Chicago RCV000192980 SCV000246356 uncertain significance not specified 2015-07-02 criteria provided, single submitter clinical testing
GeneDx RCV000767036 SCV000492097 uncertain significance not provided 2016-11-28 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALMS1 gene. The S624P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The S624P variant was not observed in approximately 6000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S624P 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. Nevertheless, this substitution occurs at a position that is not conserved across species, where P624 is wild type for at least two other mammalian species. The majority (2 out of 3) of in silico analyses predict this variant likely does not alter the protein structure/function. Lastly, while some missense variants have been reported in association with Alstrom syndrome, most pathogenic variants in ALMS1 reported to date introduce a premature termination codon (Marshall et al., 2012; Stenson et al., 2014).
Invitae RCV000801509 SCV000941286 uncertain significance Alstrom syndrome 2018-10-24 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 624 of the ALMS1 protein (p.Ser624Pro). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and proline. This variant is present in population databases (rs767987501, ExAC 0.009%). This variant has not been reported in the literature in individuals with ALMS1-related disease. ClinVar contains an entry for this variant (Variation ID: 210125). 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 proline 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.