Submissions for variant NM_001378454.1(ALMS1):c.601C>G (p.Gln201Glu)

gnomAD frequency: 0.00013  dbSNP: rs376989302

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000666004	SCV000790234	uncertain significance	Alstrom syndrome	2017-03-23	criteria provided, single submitter	clinical testing
Invitae	RCV000666004	SCV000835507	uncertain significance	Alstrom syndrome	2022-10-25	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 202 of the ALMS1 protein (p.Gln202Glu). This variant is present in population databases (rs376989302, gnomAD 0.1%). 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: 551044). 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.
Personalized Diabetes Medicine Program, University of Maryland School of Medicine	RCV001172507	SCV001335560	likely benign	Monogenic diabetes	2017-05-19	criteria provided, single submitter	research	ACMG criteria: BP4 (8 predictors), BP1 (missense in gene with truncating known) = likely benign
Ambry Genetics	RCV002352087	SCV002654604	likely benign	Cardiovascular phenotype	2022-10-14	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.
GeneDx	RCV001572852	SCV002757023	uncertain significance	not provided	2022-11-04	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV000666004	SCV003928147	uncertain significance	Alstrom syndrome		criteria provided, single submitter	research	Potent mutations in ALMS1 are associated with a rare condition called Alstrom syndrome. It can cause excessive eating, insulin resistance. However, no evidence is found to ascertain the role of rs376989302 in Alstrom syndrome yet.
Natera, Inc.	RCV000666004	SCV001457867	uncertain significance	Alstrom syndrome	2020-09-16	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001572852	SCV001797861	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001572852	SCV001922591	likely benign	not provided		no assertion criteria provided	clinical testing