ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.844C>T (p.Gln282Ter)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues RCV002814351 SCV003035389 likely pathogenic Noonan syndrome 2 2022-12-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV003167787 SCV003911670 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-12-07 criteria provided, single submitter clinical testing The p.Q282* pathogenic mutation (also known as c.844C>T), located in coding exon 9 of the LZTR1 gene, results from a C to T substitution at nucleotide position 844. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Loss-of-function variants in LZTR1 are related to an increased risk for schwannomas and autosomal recessive Noonan syndrome; however, such associations with autosomal dominant Noonan syndrome have not been observed (Piotrowski A et al. Nat Genet. 2014 Feb;46:182-7; Yamamoto GL et al. J Med Genet. 2015 Jun;52:413-21; Johnston JJ et al. Genet Med. 2018 10;20:1175-1185). Based on the supporting evidence, this variant is pathogenic for an increased risk of LZTR1-related schwannomatosis (SWN) and would be expected to cause autosomal recessive Noonan syndrome when present along with a second pathogenic or likely pathogenic variant on the other allele; however, the association of this alteration with autosomal dominant Noonan syndrome is unlikely.

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