Submissions for variant NM_001114753.3(ENG):c.694_699del (p.Arg232_Thr233del)

dbSNP: rs2131888057

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Mayo Clinic Laboratories, Mayo Clinic	RCV001508633	SCV001714911	likely pathogenic	not provided	2020-07-21	criteria provided, single submitter	clinical testing	PM2; PM4. PS4_Moderate, PP4
Ambry Genetics	RCV002368539	SCV002662233	likely pathogenic	Cardiovascular phenotype	2022-06-01	criteria provided, single submitter	clinical testing	The c.694_699delCGGACG variant (also known as p.R232_T233del) is located in coding exon 6 of the ENG gene. This variant results from an in-frame CGGACG deletion at nucleotide positions 694 to 699. This results in the in-frame deletion of arginine and threonine at codons 232 to 233. This variant has been reported in individuals and families with hereditary hemorrhagic telangiectasia (HHT) (Lesca G et al. Hum Mutat, 2004 Apr;23:289-99; McDonald J et al. Clin Genet, 2011 Apr;79:335-44). This amino acid region is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae	RCV003594129	SCV004294047	uncertain significance	Hereditary hemorrhagic telangiectasia	2023-01-17	criteria provided, single submitter	clinical testing	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. This variant disrupts a region of the ENG protein in which other variant(s) (p.Thr233del) have been observed in individuals with ENG-related conditions (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1163503). This variant has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 15024723, 21158752). This variant is not present in population databases (gnomAD no frequency). This variant, c.694_699del, results in the deletion of 2 amino acid(s) of the ENG protein (p.Arg232_Thr233del), but otherwise preserves the integrity of the reading frame.