Submissions for variant NM_000081.4(LYST):c.3311G>A (p.Arg1104Gln)

gnomAD frequency: 0.00011  dbSNP: rs148299757

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520552	SCV000618976	uncertain significance	not provided	2024-11-14	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000629208	SCV000750126	uncertain significance	Chédiak-Higashi syndrome	2022-09-27	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1104 of the LYST protein (p.Arg1104Gln). This variant is present in population databases (rs148299757, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with LYST-related conditions. ClinVar contains an entry for this variant (Variation ID: 450396). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on LYST 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.
Fulgent Genetics, Fulgent Genetics	RCV000629208	SCV000896289	uncertain significance	Chédiak-Higashi syndrome	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000629208	SCV001258775	uncertain significance	Chédiak-Higashi syndrome	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Revvity Omics, Revvity	RCV000629208	SCV003815262	uncertain significance	Chédiak-Higashi syndrome	2019-11-27	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000520552	SCV005411557	uncertain significance	not provided	2023-12-06	criteria provided, single submitter	clinical testing	PM1
Center for Computational Biology & Bioinformatics, University of California, San Diego	RCV004568670	SCV005050089	uncertain significance	Meniere disease	2024-06-03	no assertion criteria provided	research