Submissions for variant NM_006767.4(LZTR1):c.263+7_263+10del

dbSNP: rs765081424

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001175002	SCV001338499	benign	not specified	2020-04-06	criteria provided, single submitter	clinical testing	Variant summary: LZTR1 c.263+7_263+10delGAGT alters nucleotides located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00037 in 251470 control chromosomes, predominantly at a frequency of 0.0048 within the East Asian subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 960 fold of the estimated maximal expected allele frequency for a pathogenic variant in LZTR1 causing Noonan Syndrome and Related Conditions phenotype (5e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.263+7_263+10delGAGT in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
Invitae	RCV002067867	SCV002383443	benign	not provided	2024-01-24	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV002067867	SCV004152200	likely benign	not provided	2023-08-01	criteria provided, single submitter	clinical testing	LZTR1: BP4, BS2