Submissions for variant NM_006767.4(LZTR1):c.320+12C>T

gnomAD frequency: 0.00538  dbSNP: rs73879461

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000608901	SCV000728861	benign	not specified	2017-05-08	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000608901	SCV001432124	benign	not specified	2020-08-24	criteria provided, single submitter	clinical testing	Variant summary: LZTR1 c.320+12C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 3/4 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 0.0012 in 251086 control chromosomes in the gnomAD database, including 5 homozygotes. The observed variant frequency is approximately 247-fold the estimated maximal expected allele frequency for a pathogenic variant in LZTR1 causing Noonan Syndrome phenotype (5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.320+12C>T in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported in the literature. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and cited the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002066666	SCV002422403	benign	not provided	2025-02-04	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000608901	SCV001809215	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000608901	SCV001951697	benign	not specified		no assertion criteria provided	clinical testing