ClinVar Miner

Submissions for variant NM_006767.4(LZTR1):c.2023G>A (p.Gly675Arg)

gnomAD frequency: 0.00008  dbSNP: rs369362070
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001361660 SCV001557642 uncertain significance not provided 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 675 of the LZTR1 protein (p.Gly675Arg). This variant is present in population databases (rs369362070, gnomAD 0.01%). 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: 1053328). 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%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001813592 SCV002060788 uncertain significance Noonan syndrome and Noonan-related syndrome 2021-02-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002420790 SCV002717967 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-02-20 criteria provided, single submitter clinical testing The p.G675R variant (also known as c.2023G>A), located in coding exon 17 of the LZTR1 gene, results from a G to A substitution at nucleotide position 2023. The glycine at codon 675 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001361660 SCV003933158 uncertain significance not provided 2024-04-26 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Identified in individual(s) with a disorder of sex development (PMID: 36110220); This variant is associated with the following publications: (PMID: 36110220)
Baylor Genetics RCV003469596 SCV004191205 uncertain significance Schwannomatosis 2 2024-01-23 criteria provided, single submitter clinical testing

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