Submissions for variant NM_001378454.1(ALMS1):c.7129dup (p.Thr2377fs)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV002474119	SCV002770187	pathogenic	not provided	2022-12-23	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11941370)
Labcorp Genetics (formerly Invitae), Labcorp	RCV003502684	SCV004292591	pathogenic	Alstrom syndrome	2023-10-22	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Thr2378Asnfs*3) 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 Alström syndrome (PMID: 11941370). ClinVar contains an entry for this variant (Variation ID: 1806690). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003502684	SCV004813077	pathogenic	Alstrom syndrome	2024-02-05	criteria provided, single submitter	clinical testing	Variant summary: ALMS1 c.7126dupA (p.Thr2376AsnfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 249124 control chromosomes. c.7126dupA has been reported in the literature in individuals affected with Alstrom Syndrome (Hearn_2002). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 11941370). ClinVar contains an entry for this variant (Variation ID: 1806690). Based on the evidence outlined above, the variant was classified as pathogenic.