Submissions for variant NM_006767.4(LZTR1):c.719T>C (p.Met240Thr)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV003461815	SCV004191304	uncertain significance	Schwannomatosis 2	2023-08-05	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV003779049	SCV004653541	uncertain significance	not provided	2023-07-28	criteria provided, single submitter	clinical testing	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. 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. This variant has not been reported in the literature in individuals affected with LZTR1-related conditions. This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 240 of the LZTR1 protein (p.Met240Thr). This variant is not present in population databases (gnomAD no frequency).
Ambry Genetics	RCV004560178	SCV005048022	uncertain significance	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2023-09-27	criteria provided, single submitter	clinical testing	The p.M240T variant (also known as c.719T>C), located in coding exon 8 of the LZTR1 gene, results from a T to C substitution at nucleotide position 719. The methionine at codon 240 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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.