Submissions for variant NM_006767.4(LZTR1):c.1785+13_1785+33dup

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	RCV003479746	SCV004223468	benign	not specified	2023-11-07	criteria provided, single submitter	clinical testing	Variant summary: LZTR1 c.1785+13_1785+33dup21 alters nucleotides located at a position not widely known to affect splicing. Several computational tools predict a significant impact on normal splicing: Three predict the variant creates a 5' donor site, wheras one predicts the variant has no significant impact on splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00056 in 247884 control chromosomes, predominantly at a frequency of 0.0035 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 700-fold of the estimated maximal expected allele frequency for a pathogenic variant in LZTR1 causing Noonan Syndrome phenotype (5e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.1785+13_1785+33dup21 in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV003738478	SCV004565049	likely benign	not provided	2023-03-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003738478	SCV005717049	likely benign	not provided	2025-02-02	criteria provided, single submitter	clinical testing