ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.649G>T (p.Glu217Ter)

dbSNP: rs1302923931
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000681412 SCV000808875 likely pathogenic not provided 2019-10-24 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge; No data available from control populations to assess the frequency of this variant
Ambry Genetics RCV002360709 SCV002659169 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-10-14 criteria provided, single submitter clinical testing The p.E217* variant (also known as c.649G>T), located in coding exon 7 of the LZTR1 gene, results from a G to T substitution at nucleotide position 649. This changes the amino acid from a glutamic acid to a stop codon within coding exon 7. 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.
Fulgent Genetics, Fulgent Genetics RCV005027835 SCV005656732 likely pathogenic Noonan syndrome 2; LZTR1-related schwannomatosis; Noonan syndrome 10 2024-04-22 criteria provided, single submitter clinical testing

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