Submissions for variant NM_001378454.1(ALMS1):c.8674_8678del (p.Lys2892fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003305762	SCV003999432	pathogenic	Cardiovascular phenotype	2023-03-16	criteria provided, single submitter	clinical testing	The c.8677_8681delAAAGC pathogenic mutation, located in coding exon 10 of the ALMS1 gene, results from a deletion of 5 nucleotides at nucleotide positions 8677 to 8681, causing a translational frameshift with a predicted alternate stop codon (p.K2893Pfs*5). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003777124	SCV004619221	pathogenic	Alstrom syndrome	2023-09-15	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: 2561871). 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.Lys2893Profs*5) 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).