ClinVar Miner

Submissions for variant NM_001301365.1(LYST):c.3083C>G (p.Ser1028Cys) (rs150636017)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000301818 SCV000355772 uncertain significance Chédiak-Higashi syndrome 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000493084 SCV000582251 uncertain significance not provided 2017-11-22 criteria provided, single submitter clinical testing The S1028C variant in the LYST gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The S1028C variant is observed in 54/66,698 alleles (0.08%) from individuals of non-Finnish European background in the ExAC dataset (Lek et al., 2016). The S1028C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species, and in silico analysis predicts this variant likely does not alter the protein structure/function. We therefore interpret S1028C as a variant of uncertain significance.
Fulgent Genetics,Fulgent Genetics RCV000301818 SCV000896290 uncertain significance Chédiak-Higashi syndrome 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000301818 SCV000937081 uncertain significance Chédiak-Higashi syndrome 2019-12-08 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 1028 of the LYST protein (p.Ser1028Cys). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is present in population databases (rs150636017, ExAC 0.08%). This variant has not been reported in the literature in individuals with LYST-related disease. ClinVar contains an entry for this variant (Variation ID: 296408). 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 cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.

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