Submissions for variant NM_000081.4(LYST):c.8146T>G (p.Ser2716Ala)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003637959	SCV004450834	uncertain significance	Chédiak-Higashi syndrome	2024-01-08	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 2716 of the LYST protein (p.Ser2716Ala). This variant is present in population databases (rs753354686, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with LYST-related conditions. 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 LYST 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV004790588	SCV005411482	uncertain significance	not provided	2024-02-14	criteria provided, single submitter	clinical testing	BP4, PM2_moderate