Submissions for variant NM_001378454.1(ALMS1):c.11382del (p.Phe3794fs)

dbSNP: rs768759374

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000666522	SCV000790827	pathogenic	Alstrom syndrome	2017-04-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000666522	SCV001583665	pathogenic	Alstrom syndrome	2023-12-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Phe3795Leufs*38) 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 (rs768759374, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with Alström syndrome (PMID: 17594715, 29193673). ClinVar contains an entry for this variant (Variation ID: 551457). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000666522	SCV002548520	pathogenic	Alstrom syndrome	2022-05-31	criteria provided, single submitter	clinical testing	Variant summary: ALMS1 c.11379delT/p.Phe3793LeufsX38 (also known as c.11385del/p.Phe3795fs in RefSeq) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 248776 control chromosomes. c.11379delT has been reported in the literature in multiple individuals affected with Alstrom Syndrome With Dilated Cardiomyopathy or inherited retinal degeneration. These data indicate that the variant is very likely to be associated with disease. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000666522	SCV002807802	pathogenic	Alstrom syndrome	2021-10-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001701150	SCV005327054	pathogenic	not provided	2024-02-29	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 at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17594715, 25846608, 32531858, 29193673)
Clinical Genetics Laboratory, University Hospital Schleswig-Holstein	RCV000666522	SCV001745325	pathogenic	Alstrom syndrome	2021-05-17	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001701150	SCV001925026	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001701150	SCV001976083	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000666522	SCV002079010	pathogenic	Alstrom syndrome	2021-04-27	no assertion criteria provided	clinical testing