ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.1312G>T (p.Glu438Ter)

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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 RCV002385487 SCV002692036 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-10-12 criteria provided, single submitter clinical testing The p.E438* pathogenic mutation (also known as c.1312G>T), located in coding exon 12 of the LZTR1 gene, results from a G to T substitution at nucleotide position 1312. 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. In addition, this mutation has been reported in an individual with schwannomatosis (Hutter S et al. Acta Neuropathol, 2014 Sep;128:449-52; Farschtschi SC et al. Int J Mol Sci, 2020 May;21:; Godel T et al. Diagnostics (Basel), 2022 Mar;12:). 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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