Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001905687 | SCV002155980 | uncertain significance | Chédiak-Higashi syndrome | 2022-08-16 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1084 of the LYST protein (p.Ala1084Thr). This variant is present in population databases (rs376496670, gnomAD 0.003%). 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: 1386113). 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 threonine 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. |
Genome Diagnostics Laboratory, |
RCV002264416 | SCV002543624 | uncertain significance | Autoinflammatory syndrome | 2018-02-02 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002552939 | SCV003651545 | uncertain significance | Inborn genetic diseases | 2022-09-29 | criteria provided, single submitter | clinical testing | The c.3250G>A (p.A1084T) alteration is located in exon 6 (coding exon 4) of the LYST gene. This alteration results from a G to A substitution at nucleotide position 3250, causing the alanine (A) at amino acid position 1084 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV001905687 | SCV003812797 | uncertain significance | Chédiak-Higashi syndrome | 2019-06-11 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987930 | SCV004803511 | uncertain significance | not specified | 2024-01-18 | criteria provided, single submitter | clinical testing | Variant summary: LYST c.3250G>A (p.Ala1084Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250912 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3250G>A in individuals affected with Chediak-Higashi Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1386113). Based on the evidence outlined above, the variant was classified as uncertain significance. |