Submissions for variant NM_000081.4(LYST):c.3223G>A (p.Val1075Met)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002721394	SCV003007651	uncertain significance	Chédiak-Higashi syndrome	2022-09-17	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1075 of the LYST protein (p.Val1075Met). This variant is present in population databases (rs767491007, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with LYST-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
PreventionGenetics, part of Exact Sciences	RCV003395505	SCV004120992	uncertain significance	LYST-related disorder	2022-10-24	criteria provided, single submitter	clinical testing	The LYST c.3223G>A variant is predicted to result in the amino acid substitution p.Val1075Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0026% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-235969213-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.