Submissions for variant NM_001114753.3(ENG):c.512G>C (p.Arg171Pro)

dbSNP: rs756980265

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000523480	SCV000618265	uncertain significance	not provided	2017-07-10	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the ENG gene. The R171P variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R171P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, this substitution occurs at a position that is not conserved across species.
Ambry Genetics	RCV003278865	SCV004005053	likely pathogenic	Cardiovascular phenotype	2023-06-06	criteria provided, single submitter	clinical testing	The p.R171P variant (also known as c.512G>C), located in coding exon 4 of the ENG gene, results from a G to C substitution at nucleotide position 512. The arginine at codon 171 is replaced by proline, an amino acid with dissimilar properties. This alteration has been reported in individuals with hereditary hemorrhagic telangiectasia (HHT), including segregating with disease in two families (Heimdal K et al. Clin Genet, 2016 Feb;89:182-6; external communication). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.