Submissions for variant NM_001807.6(CEL):c.878C>T (p.Pro293Leu)

gnomAD frequency: 0.00020  dbSNP: rs201066180

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001773953	SCV001994403	uncertain significance	not provided	2019-08-26	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genomics Laboratory, Virgen de la Arrixaca University Clinical Hospital	RCV004797952	SCV005419198	uncertain significance	Maturity-onset diabetes of the young type 8	2024-11-14	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV003151349	SCV003839341	uncertain significance	not specified	2022-09-06	no assertion criteria provided	clinical testing	DNA sequence analysis of the CEL gene demonstrated a sequence change, c.878C>T, in exon 7 that results in an amino acid change, p.Pro293Leu. This sequence change does not appear to have been previously described in individuals with CEL-related disorders. This sequence change has been described in the gnomAD database with a frequency of 0.024% in the European subpopulation (dbSNP rs201066180). The p.Pro293Leu change affects a poorly conserved amino acid residue located in a domain of the CEL protein that is known to be functional. The p.Pro293Leu substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Pro293Leu change remains unknown at this time. Heterozygous pathogenic variants in the CEL gene are associated with maturity –onset diabetes of the young, type 8 (OMIM# 609812).