ClinVar Miner

Submissions for variant NM_000081.4(LYST):c.5290G>A (p.Gly1764Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001864848 SCV002124602 uncertain significance Chédiak-Higashi syndrome 2024-10-16 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1764 of the LYST protein (p.Gly1764Ser). This variant is present in population databases (rs749778166, gnomAD 0.02%). 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: 1359937). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Neuberg Centre For Genomic Medicine, NCGM RCV001864848 SCV005042578 uncertain significance Chédiak-Higashi syndrome criteria provided, single submitter clinical testing The missense c.5290G>A p.Gly1764Ser variant in the LYST gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant has allele frequency 0.002% in gnomAD Exomes and is novel not in any individuals in 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance. However, no details are available for independent assessment. The amino acid Glycine at position 1764 is changed to a Serine changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Gly1764Ser in LYST is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.

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