ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.2032C>T (p.Arg678Trp)

gnomAD frequency: 0.00004  dbSNP: rs780217270
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001907682 SCV002130685 uncertain significance not provided 2024-01-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 678 of the LZTR1 protein (p.Arg678Trp). This variant is present in population databases (rs780217270, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with LZTR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1364777). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LZTR1 protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV002422918 SCV002721851 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2023-12-30 criteria provided, single submitter clinical testing The c.2032C>T (p.R678W) alteration is located in exon 17 (coding exon 17) of the LZTR1 gene. This alteration results from a C to T substitution at nucleotide position 2032, causing the arginine (R) at amino acid position 678 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV001907682 SCV002762597 uncertain significance not provided 2022-06-09 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics RCV003470975 SCV004191301 uncertain significance Schwannomatosis 2 2023-08-07 criteria provided, single submitter clinical testing

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