Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000055735 | SCV003524127 | uncertain significance | Chédiak-Higashi syndrome | 2022-04-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1563 of the LYST protein (p.Arg1563His). This variant also falls at the last nucleotide of exon 13, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Chediak-Higashi syndrome (PMID: 22883044). ClinVar contains an entry for this variant (Variation ID: 3816). 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
OMIM | RCV000004020 | SCV000024186 | pathogenic | Chediak-Higashi syndrome, adult type | 2002-02-15 | no assertion criteria provided | literature only | |
Gene |
RCV000055735 | SCV000086673 | not provided | Chédiak-Higashi syndrome | no assertion provided | literature only |