ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.1291G>T (p.Glu431Ter)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002380556 SCV002692829 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-12-27 criteria provided, single submitter clinical testing The p.E431* variant (also known as c.1291G>T), located in coding exon 12 of the LZTR1 gene, results from a G to T substitution at nucleotide position 1291. This changes the amino acid from a glutamic acid to a stop codon within coding exon 12. 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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