Submissions for variant NM_001365276.2(TNXB):c.2030A>G (p.Asp677Gly)

gnomAD frequency: 0.00158  dbSNP: rs141190850

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000762400	SCV000577592	likely benign	not provided	2021-03-11	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32164334, 31141158, 32214361)
CeGaT Center for Human Genetics Tuebingen	RCV000762400	SCV000892713	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	TNXB: BS2
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768116	SCV000899041	uncertain significance	Ehlers-Danlos syndrome due to tenascin-X deficiency; Vesicoureteral reflux 8	2021-03-30	criteria provided, single submitter	clinical testing	TNXB NM_019105.6 exon 3 p.Asp677Gly (c.2030A>G): This variant has not been reported in the literature but is present in 0.4% (118/25154) of European (Finnish) alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs141190850). This variant is present in ClinVar (Variation ID:426989). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Baylor Genetics	RCV001335021	SCV001528052	uncertain significance	Ehlers-Danlos syndrome due to tenascin-X deficiency	2018-12-24	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002279264	SCV002566217	likely benign	Ehlers-Danlos syndrome	2022-03-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002420250	SCV002718711	uncertain significance	Cardiovascular phenotype	2021-07-03	criteria provided, single submitter	clinical testing	The p.D677G variant (also known as c.2030A>G), located in coding exon 2 of the TNXB gene, results from an A to G substitution at nucleotide position 2030. The aspartic acid at codon 677 is replaced by glycine, an amino acid with similar properties. This alteration has been reported in cohorts of subjects with cervical insufficiency, congenital anomalies of the kidney and urinary tract, and Ehlers-Danlos syndrome (Angwin C et al. Br J Dermatol, 2020 03;182:698-707; Ahn YH et al. J Clin Med, 2020 Mar;9:; Volozonoka L et al. PLoS One, 2020 Mar;15:e0230771). This amino acid position is highly 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000762400	SCV004227224	uncertain significance	not provided	2023-03-30	criteria provided, single submitter	clinical testing	BS1
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000762400	SCV001808426	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000762400	SCV001929065	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000762400	SCV001974117	likely benign	not provided		no assertion criteria provided	clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV001335021	SCV004171651	uncertain significance	Ehlers-Danlos syndrome due to tenascin-X deficiency	2023-11-24	no assertion criteria provided	clinical testing