Description
Given its frequency in a large number of controls, no case data, and the autosomal recessive inheritance pattern of the associated disease, we consider this variant a variant of uncertain significance likely benign, and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). The variant has not been seen in any cases of atrial fibrillation or ALMS1-related disease. Testing for our patient was performed at Invitae. The ALMS1 gene is associated with autosomal recessive Alström syndrome. Alström syndrome includes cone-rod dystrophy, obesity, progressive sensorineural hearing impairment, dilated or restrictive cardiomyopathy, the insulin resistance syndrome, and multiple organ failure. Our patient was only found to have one variant in this gene and does not have a phenotype consistent with this condition. This sequence change replaces tyrosine with cysteine at codon 680 of the ALMS1 protein (p.Tyr680Cys). The tyrosine residue is weakly conserved and there is a large physicochemical di erence between tyrosine and cysteine. Algorithms developed to predict the e ect of missense changes on protein structure and function do not agree on the potential impact of this missense change. The variant is present in 422 of 140,893 (MAF = 0.15%) total individuals in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Latino, and Ashkenazi descent. Specifically, the variant is present in 292 of 63,046 European Non-Finnish individuals (MAF= 0.23%).
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
