Submissions for variant NM_001365276.2(TNXB):c.211G>T (p.Val71Leu)

gnomAD frequency: 0.00031  dbSNP: rs201922477

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000585373	SCV000344236	uncertain significance	not provided	2016-07-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000585373	SCV000693208	uncertain significance	not provided	2024-02-01	criteria provided, single submitter	clinical testing	TNXB: PM2
GeneDx	RCV000585373	SCV001764030	uncertain significance	not provided	2024-05-21	criteria provided, single submitter	clinical testing	Reported in a family in which two individuals were reported to be heterozygous for the variant; one patient with joint hypermobility and the other patient with bilateral vesicoureteral reflux (PMID: 26408188); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 26408188)
Ambry Genetics	RCV002418132	SCV002726441	uncertain significance	Cardiovascular phenotype	2024-11-18	criteria provided, single submitter	clinical testing	The p.V71L variant (also known as c.211G>T), located in coding exon 1 of the TNXB gene, results from a G to T substitution at nucleotide position 211. The valine at codon 71 is replaced by leucine, an amino acid with highly similar properties. This variant has been reported in the heterozygous state in two relatives with vesicoureteral reflux (Elahi S et al. Pediatr Nephrol, 2016 Feb;31:247-53). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002487274	SCV002793727	uncertain significance	Ehlers-Danlos syndrome due to tenascin-X deficiency; Vesicoureteral reflux 8	2021-07-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000585373	SCV004264920	uncertain significance	not provided	2023-12-05	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 71 of the TNXB protein (p.Val71Leu). This variant is present in population databases (rs201922477, gnomAD 0.05%). This missense change has been observed in individual(s) with vesicoureteral reflux (PMID: 26408188). ClinVar contains an entry for this variant (Variation ID: 289817). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000585373	SCV005412122	uncertain significance	not provided	2024-06-28	criteria provided, single submitter	clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV003333746	SCV004041746	uncertain significance	Ehlers-Danlos syndrome due to tenascin-X deficiency	2023-10-09	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004751443	SCV005356257	uncertain significance	TNXB-related disorder	2024-07-02	no assertion criteria provided	clinical testing	The TNXB c.211G>T variant is predicted to result in the amino acid substitution p.Val71Leu. This variant has been reported in an individual with vesicoureteral reflux (Elahi et al. 2016. PubMed ID: 26408188). This variant is reported in 0.056% of alleles in individuals of European (Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.