ClinVar Miner

Submissions for variant NM_001083116.3(PRF1):c.1120T>G (p.Trp374Gly)

dbSNP: rs1060499556
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Dr. Faghihi's Medical Genetic Center RCV000449644 SCV000502989 likely pathogenic Familial hemophagocytic lymphohistiocytosis 2 no assertion criteria provided research Following evidences confirm that this mutation can lead to FHL2: 1-Whole exome sequencing only identified this mutation to be the main cause of FHL2 in the patient. 2- Sanger sequencing confirmed the mutation in the proband and on the basis of identified heterozygous mutation in his parents, the inheritance pattern must be an autosomal recessive mode. 3- Bioinformatics software such as polyphen, SIFT, LRT, Mutation Taster, FATHMM, Radial SVM and Mutation Assessor software are predicted that this variant will be damaging (Table 2) 4- The comparative amino acids alignment of perforin 1 protein across all Kingdoms using multiple sequence alignment analysis using T-Coffee Multiple Sequence Alignment Program revealed that this amino acid is highly conserved during evolution. 5. In addition, a substitution from tryptophan amino acid with an aromatic side chain (at position 374) to glycine amino acid with a nonpolar and small hydrogen side chain can make a major problem in the protein. As a result, this mutation in PRF1 gene is extremely pathogenic in our patient with FHL2.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.