ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.790G>A (p.Asp264Asn)

gnomAD frequency: 0.00001  dbSNP: rs1210433339
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002422874 SCV002677268 uncertain significance Cardiovascular phenotype 2021-04-23 criteria provided, single submitter clinical testing The p.D264N variant (also known as c.790G>A), located in coding exon 6 of the ENG gene, results from a G to A substitution at nucleotide position 790. The aspartic acid at codon 264 is replaced by asparagine, an amino acid with highly similar properties. This variant has been reported in individuals with a clinical diagnosis of hereditary hemorrhagic telangiectasia (Letteboer TG et al. Hum. Genet., 2005 Jan;116:8-16; Prigoda NL et al. J Med Genet, 2006 Sep;43:722-8; Lenato GM et al. Hum. Mutat., 2006 Feb;27:213-4). In a functional study, D264N was predominantly localized to the plasma membrane, similar to wild-type endoglin (Ali BR et al. PLoS ONE, 2011 Oct;6:e26206). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV002545229 SCV003212471 uncertain significance Hereditary hemorrhagic telangiectasia 2024-06-03 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 264 of the ENG protein (p.Asp264Asn). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 15517393, 16429404, 35587316, 36588762). ClinVar contains an entry for this variant (Variation ID: 1342710). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ENG protein function with a negative predictive value of 95%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on ENG function (PMID: 22022569). 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.
Diagnostics Division, CENTRE FOR DNA FINGERPRINTING AND DIAGNOSTICS RCV001839470 SCV002099436 likely pathogenic Telangiectasia, hereditary hemorrhagic, type 1 2018-02-09 no assertion criteria provided clinical testing

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