ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.59C>T (p.Ala20Val)

gnomAD frequency: 0.00001  dbSNP: rs770762358
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523878 SCV000621016 uncertain significance not provided 2017-09-18 criteria provided, single submitter clinical testing The A20V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A20V variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). It is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved and in silico analysis predicts this variant likely does not alter the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Baylor Genetics RCV001788275 SCV002030176 uncertain significance Noonan syndrome 10 2021-10-26 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV000523878 SCV002223420 uncertain significance not provided 2023-12-27 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 20 of the LZTR1 protein (p.Ala20Val). This variant is present in population databases (rs770762358, gnomAD 0.001%). 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: 452228). 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 RCV002358417 SCV002657157 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-03-09 criteria provided, single submitter clinical testing The p.A20V variant (also known as c.59C>T), located in coding exon 1 of the LZTR1 gene, results from a C to T substitution at nucleotide position 59. The alanine at codon 20 is replaced by valine, an amino acid with similar properties. This amino acid position is 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.
Baylor Genetics RCV004568673 SCV005060660 uncertain significance Schwannomatosis 2 2024-01-20 criteria provided, single submitter clinical testing

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