Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000669201 | SCV000793930 | pathogenic | Alstrom syndrome | 2017-09-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000669201 | SCV001215912 | pathogenic | Alstrom syndrome | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser3873Tyrfs*19) 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 present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with ALMS1-related conditions (PMID: 26111748, 26969326, 29588463). ClinVar contains an entry for this variant (Variation ID: 553694). For these reasons, this variant has been classified as Pathogenic. |
Blueprint Genetics | RCV001075531 | SCV001241157 | pathogenic | Retinal dystrophy | 2018-12-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002369802 | SCV002626138 | pathogenic | Cardiovascular phenotype | 2021-08-23 | criteria provided, single submitter | clinical testing | The c.11618_11619delCT pathogenic mutation, located in coding exon 17 of the ALMS1 gene, results from a deletion of two nucleotides at nucleotide positions 11618 to 11619, causing a translational frameshift with a predicted alternate stop codon (p.S3873Yfs*19). This mutation has been detected with other mutations in the ALMS1 gene in several individuals with Alstrom syndrome (Nadol JB et al. Audiol Neurootol, 2015 Jun;20:267-72; Citton V et al. J Neuroradiol, 2016 Jun;43:195-9; Sloan-Heggen CM et al. Hum Genet, 2016 Apr;135:441-450; Sanchez-Navarro I et al. Sci Rep, 2018 03;8:5285; Bea-Mascato B et al. Genes (Basel), 2021 02;12). 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, |
RCV000669201 | SCV001455026 | pathogenic | Alstrom syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |