Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001175428 | SCV001338977 | benign | not specified | 2020-03-23 | criteria provided, single submitter | clinical testing | Variant summary: LZTR1 c.1620T>C alters a non-conserved nucleotide resulting in a synonymous change. 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 0.00053 in 279654 control chromosomes, predominantly at a frequency of 0.0055 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1100 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 African or African-American origin. To our knowledge, no occurrence of c.1620T>C 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. |
| Labcorp Genetics |
RCV001520899 | SCV001730112 | benign | not provided | 2024-01-31 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001520899 | SCV001794523 | likely benign | not provided | 2021-03-04 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002402525 | SCV002708043 | likely benign | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2020-08-05 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
| Fulgent Genetics, |
RCV002497610 | SCV002808606 | likely benign | Noonan syndrome 2; Schwannomatosis 2; Noonan syndrome 10 | 2022-04-05 | criteria provided, single submitter | clinical testing |