Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002049361 | SCV002116736 | pathogenic | Alstrom syndrome | 2022-07-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1351997). This premature translational stop signal has been observed in individual(s) with Alström syndrome (PMID: 17594715). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Ser1142*) 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). |
| Ambry Genetics | RCV004631757 | SCV005127436 | pathogenic | Cardiovascular phenotype | 2024-04-04 | criteria provided, single submitter | clinical testing | The p.S1142* pathogenic mutation (also known as c.3425C>G), located in coding exon 8 of the ALMS1 gene, results from a C to G substitution at nucleotide position 3425. This changes the amino acid from a serine to a stop codon within coding exon 8. This variant has been identified in the homozygous state in individual(s) with features consistent with Alström syndrome (Marshall JD et al. Hum Mutat, 2007 Nov;28:1114-23; Zulato E et al. PLoS One, 2011 Apr;6:e19081). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |