Submissions for variant NM_001844.5(COL2A1):c.2965C>T (p.Arg989Cys) (rs121912874)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478360	SCV000568538	pathogenic	not provided	2018-08-02	criteria provided, single submitter	clinical testing	The R989C variant in the COL2A1 gene has been reported previously using alternate nomenclature R789C in individuals with spondyloepiphyseal dysplasia congenita (Chan et al., 1993; Nishimura et al., 2005; Hoornaert et al., 2006). The R989C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R989C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. Functional studies using an inducible expression system for expressing R989C, showed that even a small amount of the R989C mutant collagen would induce aberrations in the cell/matrix systems (Jensen et al., 2011). We interpret R989C as a pathogenic variant.
Fulgent Genetics,Fulgent Genetics	RCV000762895	SCV000893295	pathogenic	Achondrogenesis type II; Avascular necrosis of the head of femur; Epiphyseal dysplasia, multiple, with myopia and conductive deafness; Coxa plana; Kniest dysplasia; Osteoarthritis with mild chondrodysplasia; Spondyloperipheral dysplasia-short ulna syndrome; Stickler syndrome type 1; Platyspondylic dysplasia, Torrance type; Spondylometaphyseal dysplasia; Spondyloepiphyseal dysplasia congenita; Czech dysplasia, metatarsal type; Stickler syndrome, type I, nonsyndromic ocular; Spondyloepiphyseal dysplasia, stanescu type	2018-10-31	criteria provided, single submitter	clinical testing
Institute of Human Genetics,Klinikum rechts der Isar	RCV000995718	SCV001150043	pathogenic	Spondyloperipheral dysplasia-short ulna syndrome	2019-05-27	criteria provided, single submitter	clinical testing
OMIM	RCV000018910	SCV000039194	pathogenic	Spondyloepiphyseal dysplasia congenita	1997-01-01	no assertion criteria provided	literature only

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