ClinVar Miner

Submissions for variant NM_025077.4(TOE1):c.551G>T (p.Arg184Leu)

dbSNP: rs267598623
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
Department of Medical Genetics, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine RCV001682617 SCV001895909 likely pathogenic Pontocerebellar hypoplasia type 7 2021-09-19 criteria provided, single submitter clinical testing The c.551G>T, p.Arg184Leu variant was identified in a Chinese patient with PCH7, who yet harbored another heterozygous splicing variant of c.237-2A>G . The splicing variant was inherited from mother, while the missense variant was de novo. TA clone sequencing confirmed the missense variant occurred on the paternal strand of the patient. The c.551G>T, p.Arg184Leu variant located at exon 6 of TOE1 was not present in the gnomAD database and has not been previously reported. Sequence analysis showed that the amino acid residue at position 184 is located within the Asp-Glu-Asp-Asp (DEDD) deadenylase domain, a mutation hotspot of TOE1. Conservation analysis indicates Arg 184 is highly conserved among various species.Moreover, analysis of the 3D structure revealed that this arginine to leucine mutation may disrupt the proper formation of the β-sheet in the secondary structure of TOE1 protein. VarCards predicted that the p.Arg184Leu variant would impair TOE1 function, according to SIFT (“Damaging”, score = 0.01), PolyPhen-2 (“Possibly damaging”, score = 0.89), MutationTaster (“Disease-causing”, score = 0.87), ClinPred (“Pathogenic”, score = 0.96), and CADD (“Damaging”, score = 24). According to the ACMG/AMP 2015 guideline (Richards et al., 2015), the c.551G>T, p.Arg184Leu variant was classified as likely pathogenic (PM1+ PM2+PM3+PP3).

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.