ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.1904C>T (p.Pro635Leu) (rs148677674)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001454598 SCV001658330 likely benign not provided 2020-02-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001584206 SCV001821411 likely benign not specified 2021-08-28 criteria provided, single submitter clinical testing Variant summary: LZTR1 c.1904C>T (p.Pro635Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00016 in 250026 control chromosomes. The observed variant frequency is approximately 31 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 benign. To our knowledge, no occurrence of c.1904C>T in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic and one laboratory classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000499922 SCV000590942 likely pathogenic Noonan syndrome 10 2017-04-26 no assertion criteria provided clinical testing This mutation has been reported in 1000 genomes and ExAC databases with allele frequency 0.04% and 0.022%. However, this variant is reported as damaging by SIFT, LRT and MutationTaster.

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