ClinVar Miner

Submissions for variant NM_058172.6(ANTXR2):c.134T>C (p.Leu45Pro) (rs886041401)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000369962 SCV000330000 pathogenic not provided 2017-05-12 criteria provided, single submitter clinical testing The L45P variant in the ANTXR2 gene has been reported previously as a homozygous pathogenic variant in two affected individuals of Bedouian ancestry from the same family, and also in another unrelated individual of Saudi ancestry, all with infantile systemic hyalinosis (Hanks et al., 2003; Mohamed et al., 2014). The L45P variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The L45P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs within the von Willebrand A domain at a position that is conserved across species. In vitro functional studies demonstrated that this variant led to retention of the protein in the endoplasmic reticulum (ER); the studies suggested that this variant results in misfolding which causes the ER retention (Deuquet et al., 2009). Therefore, we interpret L45P as a pathogenic variant.
Pathology and Clinical Laboratory Medicine,King Fahad Medical City RCV001261563 SCV001438829 pathogenic Hyaline fibromatosis syndrome criteria provided, single submitter clinical testing
Baylor Genetics RCV001261563 SCV001523658 pathogenic Hyaline fibromatosis syndrome 2020-06-03 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Biochemical Molecular Genetic Laboratory,King Abdulaziz Medical City RCV001261563 SCV001469151 likely pathogenic Hyaline fibromatosis syndrome 2020-11-12 no assertion criteria provided clinical testing

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