ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.1620T>C (p.His540=)

dbSNP: rs141610191
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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.
Invitae RCV001520899 SCV001730112 benign not provided 2024-01-31 criteria provided, single submitter clinical testing
GeneDx 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, Fulgent Genetics RCV002497610 SCV002808606 likely benign Noonan syndrome 2; Schwannomatosis 2; Noonan syndrome 10 2022-04-05 criteria provided, single submitter clinical testing

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