Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001260420 | SCV001437412 | benign | not specified | 2020-09-08 | criteria provided, single submitter | clinical testing | Variant summary: LZTR1 c.652-10C>A 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. 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 0.00056 in 251174 control chromosomes, predominantly at a frequency of 0.00057 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 114 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 Non-Finnish European origin. To our knowledge, no occurrence of c.652-10C>A in individuals affected with Noonan Syndrome 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. |
Labcorp Genetics |
RCV001519192 | SCV001728019 | benign | not provided | 2025-02-02 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001519192 | SCV001802510 | likely benign | not provided | 2020-08-04 | criteria provided, single submitter | clinical testing | |
Institute for Clinical Genetics, |
RCV001519192 | SCV002009527 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV005360003 | SCV005914436 | likely benign | LZTR1-related schwannomatosis | 2022-08-17 | criteria provided, single submitter | clinical testing |