Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001384455 | SCV001583954 | pathogenic | Alstrom syndrome | 2021-11-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp3521Asnfs*25) 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: 1071886). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002404899 | SCV002713509 | pathogenic | Cardiovascular phenotype | 2022-06-08 | criteria provided, single submitter | clinical testing | The c.10561_10564delGACA variant, located in coding exon 16 of the ALMS1 gene, results from a deletion of 4 nucleotides at nucleotide positions 10561 to 10564, causing a translational frameshift with a predicted alternate stop codon (p.D3521Nfs*25). This variant was reported in two individuals from an Alstrom syndrome cohort (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. |