ClinVar Miner

Submissions for variant NM_001365276.2(TNXB):c.6074A>T (p.Asp2025Val)

gnomAD frequency: 0.00056  dbSNP: rs201397168
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UCLA Clinical Genomics Center, UCLA RCV000199167 SCV000255492 likely pathogenic Ehlers-Danlos syndrome, type 3 2013-02-05 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000998564 SCV001154694 likely benign not provided 2023-08-01 criteria provided, single submitter clinical testing TNXB: BP4, BS2
GeneDx RCV000998564 SCV001772399 likely benign not provided 2021-06-22 criteria provided, single submitter clinical testing Reported as a single heterozygous variant in association with joint pain, hypermobility, chronic muscle weakness, and Raynaud's phenomenon (Lee et al., 2014; Kaufman et al., 2016); however no segregation data is available, and at least one patient is Ashkenazi Jewish; This variant is associated with the following publications: (PMID: 31589614, 26582918, 25326637, 28344932)
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002277552 SCV002566291 uncertain significance Ehlers-Danlos syndrome 2022-02-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV002354569 SCV002659762 benign Cardiovascular phenotype 2019-05-03 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.
Reproductive Health Research and Development, BGI Genomics RCV000199167 SCV001142356 uncertain significance Ehlers-Danlos syndrome, type 3 2020-01-06 no assertion criteria provided curation NM_019105.6:c.6074A>T in the TNXB gene has an allele frequency of 0.018 in Ashkenazi Jewish subpopulation in the gnomAD database. Pathogenic computational verdict because pathogenic predictions from DANN, EIGEN, FATHMM-MKL, MutationTaster and SIFT. It has been detected in heterozygous state in one individual with Ehlers-Danlos syndrome (PMID: 25326637). We interpret it as variant of uncertain significance (VUS). ACMG/AMP criteria applied: PP3; PP4.

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