ClinVar Miner

Submissions for variant NM_001301365.1(LYST):c.8806G>A (p.Val2936Ile) (rs2753327)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000629187 SCV000750103 uncertain significance Chédiak-Higashi syndrome 2019-12-17 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 2936 of the LYST protein (p.Val2936Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs2753327, ExAC 0.1%). This variant has not been reported in the literature in individuals with LYST-related disease. ClinVar contains an entry for this variant (Variation ID: 525145). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneDx RCV000658240 SCV000780011 uncertain significance not provided 2018-05-29 criteria provided, single submitter clinical testing The V2936I variant in the LYST gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V2936I variant is observed in 39/34404 (0.11%) alleles from individuals of Latino background, in large population cohorts (Lek et al., 2016). The V2936I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret V2936I as a variant of uncertain significance.
Fulgent Genetics,Fulgent Genetics RCV000629187 SCV000894771 uncertain significance Chédiak-Higashi syndrome 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000629187 SCV001256311 uncertain significance Chédiak-Higashi syndrome 2017-04-27 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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