Submissions for variant NM_019098.5(CNGB3):c.1492T>A (p.Leu498Met)

gnomAD frequency: 0.00350  dbSNP: rs115246141

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000480707	SCV000570660	uncertain significance	not provided	2016-06-10	criteria provided, single submitter	clinical testing	The L498M variant in the CNGB3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The NHLBI ESP Exome Sequencing Project reports L498M was observed in 52/4406 (1.2%) alleles from individuals of African American background, with one homozygous individual reported, indicating it may be a rare benign variant in this population. The L498M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Leucine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret L498M as a variant of uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV000764781	SCV000895925	uncertain significance	Achromatopsia 3; Severe early-childhood-onset retinal dystrophy	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000480707	SCV001049189	benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001276131	SCV001461982	benign	Achromatopsia	2019-11-11	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004535518	SCV004742573	benign	CNGB3-related disorder	2019-10-25	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).