Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001264472 | SCV001442646 | likely benign | not specified | 2020-10-19 | criteria provided, single submitter | clinical testing | Variant summary: LZTR1 c.594-3C>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. 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 0.00015 in 250884 control chromosomes, predominantly at a frequency of 0.002 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 400 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 African or African-American origin. To our knowledge, no occurrence of c.594-3C>T 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 likely benign. |
Baylor Genetics | RCV001330296 | SCV001521937 | uncertain significance | Noonan syndrome 2 | 2019-08-17 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Invitae | RCV001401433 | SCV001603256 | likely benign | not provided | 2024-01-27 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001401433 | SCV001751986 | likely benign | not provided | 2018-07-12 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002357064 | SCV002647606 | benign | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-10-28 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |