Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000672392 | SCV000797491 | likely pathogenic | Alstrom syndrome | 2018-01-26 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000672392 | SCV001592097 | pathogenic | Alstrom syndrome | 2023-11-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp2459Alafs*18) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Alstrom syndrome (PMID: 25846608). ClinVar contains an entry for this variant (Variation ID: 556391). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002386150 | SCV002672093 | pathogenic | Cardiovascular phenotype | 2023-09-07 | criteria provided, single submitter | clinical testing | The c.7376_7379delATAG pathogenic mutation, located in coding exon 8 of the ALMS1 gene, results from a deletion of 4 nucleotides at nucleotide positions 7376 to 7379, causing a translational frameshift with a predicted alternate stop codon (p.D2459Afs*18). In a cohort of individuals with Alstrom syndrome, this mutation was identified in 2 alleles (Marshall JD et al. Hum. Mutat., 2015 Jul;36:660-8). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Natera, |
RCV000672392 | SCV002082868 | pathogenic | Alstrom syndrome | 2021-09-02 | no assertion criteria provided | clinical testing |