Submissions for variant NM_001114753.3(ENG):c.640G>A (p.Gly214Ser)

gnomAD frequency: 0.00034  dbSNP: rs150932144

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000859971	SCV000546132	likely benign	Hereditary hemorrhagic telangiectasia	2024-11-12	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000457880	SCV000883141	uncertain significance	Telangiectasia, hereditary hemorrhagic, type 1	2018-11-21	criteria provided, single submitter	clinical testing
Mendelics	RCV000457880	SCV001137909	uncertain significance	Telangiectasia, hereditary hemorrhagic, type 1	2019-05-28	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000457880	SCV001530111	uncertain significance	Telangiectasia, hereditary hemorrhagic, type 1	2018-04-26	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported in patients with hemorrhagic telangiectasia [PMID 16754821] and pulmonary arterial hypertension [PMID: 23298310]
Ambry Genetics	RCV003298151	SCV003999986	benign	Cardiovascular phenotype	2023-04-10	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003407567	SCV004115171	uncertain significance	ENG-related disorder	2023-06-02	criteria provided, single submitter	clinical testing	The ENG c.640G>A variant is predicted to result in the amino acid substitution p.Gly214Ser. This variant was reported in an individual with hereditary hemorrhagic telangiectasia (HHT) and was also found in the patient's asymptomatic mother (Mei-Zahav et al 2006. PubMed ID: 16754821). This variant was reported in a patient with pulmonary arterial hypertension (PAH) and also detected in two unaffected family members (Family 8 in Pfarr et al 2013. PubMed ID: 23298310). This variant is reported in 0.093% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-130588023-C-T), which is higher than expected to be consistent with a highly penetrant causative variant. In ClinVar, this variant has conflicting interpretations regarding its pathogenicity ranging from likely benign to pathogenic (https://preview.ncbi.nlm.nih.gov/clinvar/variation/161233/). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
CSER _CC_NCGL, University of Washington	RCV000148487	SCV000190190	uncertain significance	Haemorrhagic telangiectasia 1	2014-06-01	no assertion criteria provided	research
Rare Disease Genomics Group, St George's University of London	RCV000488867	SCV000576352	pathogenic	Pulmonary hypertension, primary, 1		no assertion criteria provided	literature only