Submissions for variant NM_001378454.1(ALMS1):c.2617C>T (p.Gln873Ter)

dbSNP: rs1572932845

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001008004	SCV001167736	pathogenic	not provided	2019-02-11	criteria provided, single submitter	clinical testing	The Q874X variant in the ALMS1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q874X variant is not observed in large population cohorts (Lek et al., 2016). We interpret Q874X as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001860585	SCV002163546	pathogenic	Alstrom syndrome	2022-11-18	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: 816972). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln874*) 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).