ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.1342G>A (p.Val448Met)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002387742 SCV002691914 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-10-19 criteria provided, single submitter clinical testing The p.V448M variant (also known as c.1342G>A), located in coding exon 12 of the LZTR1 gene, results from a G to A substitution at nucleotide position 1342. The valine at codon 448 is replaced by methionine, an amino acid with highly similar properties. The variant has been detected in a cohort of patients with myeloid malignancy (Li ST et al. Leukemia, 2020 06;34:1675-1678). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003095002 SCV003244319 uncertain significance not provided 2022-06-28 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 448 of the LZTR1 protein (p.Val448Met). This variant is present in population databases (rs750902731, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with LZTR1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Baylor Genetics RCV004572407 SCV005060662 uncertain significance Schwannomatosis 2 2024-01-14 criteria provided, single submitter clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund RCV003095002 SCV005198703 uncertain significance not provided 2023-11-17 criteria provided, single submitter clinical testing

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