Submissions for variant NM_001378454.1(ALMS1):c.11411G>C (p.Arg3804Thr)

gnomAD frequency: 0.00019  dbSNP: rs201028172

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000434442	SCV000533350	uncertain significance	not provided	2023-03-23	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign in association with an ALMS1-related disorder to our knowledge; This variant is associated with the following publications: (PMID: 31199839)
Invitae	RCV000548287	SCV000631757	uncertain significance	Alstrom syndrome	2022-11-01	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 3805 of the ALMS1 protein (p.Arg3805Thr). This variant is present in population databases (rs201028172, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 390504). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics	RCV000548287	SCV000897048	uncertain significance	Alstrom syndrome	2018-10-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002451038	SCV002615567	likely benign	Cardiovascular phenotype	2022-03-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000434442	SCV004155010	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	ALMS1: BP4
Natera, Inc.	RCV000548287	SCV002079012	uncertain significance	Alstrom syndrome	2021-07-20	no assertion criteria provided	clinical testing