Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Diagnostics Services |
RCV001527403 | SCV001738396 | pathogenic | Chédiak-Higashi syndrome | 2021-05-13 | criteria provided, single submitter | clinical testing | The c.4322_4325del variant is not present in publicly available population databases like1000 Genomes,Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD) or in the Indian Exome Database [Kausthubham et al. Hum Mutat, 2021] and our in-house exome database. The variant has never been previosuly reported to ClinVar, Human Genome Mutation Database (HGMD) or OMIM databases in affected individuals. In-silico pathogenicity prediction programs like MutationTaster2, CADD, Varsome etc. predicted this variant to be likely disease causing.The variant causes frameshift at 1441 amino acid of the wild-type transcript,leading to a premature stop codon at the 1452 amino acid of the altered transcript, resulting either in a truncated protein or nonsense mediated decay of the mRNA. The variant qualifies all the criteria of ACMG guidelines to be classified as pathogenic. |
Labcorp Genetics |
RCV001527403 | SCV004311577 | pathogenic | Chédiak-Higashi syndrome | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu1441Valfs*12) in the LYST gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LYST are known to be pathogenic (PMID: 9215679, 11857544). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LYST-related conditions. For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV001527403 | SCV005646625 | pathogenic | Chédiak-Higashi syndrome | 2024-06-22 | criteria provided, single submitter | clinical testing |