Submissions for variant NM_000089.3(COL1A2):c.982G>A (p.Gly328Ser) (rs66612022)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000545434	SCV000627364	pathogenic	Ehlers-Danlos syndrome, classic type; Osteogenesis imperfecta type I	2019-04-18	criteria provided, single submitter	clinical testing	This sequence change replaces glycine with serine at codon 328 of the COL1A2 protein (p.Gly328Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with osteogenesis imperfecta (OI) (PMID: 7860070, 22589248, 9272740, 16705691), and is a well-known cause of OI types III and IV (reviewed in PMID: 17078022). This variant is also known as p.Gly238Ser in the literature. Variants that affect the glycine residue in Gly-Xaa-Yaa repeats of the collagen triple helix are known to disrupt protein folding and stability. Experimental studies have shown that this missense variant results in the production of abnormal COL1A2 protein (PMID: 9272740, 7860070, 9594376). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics	RCV000763174	SCV000893765	pathogenic	Osteogenesis imperfecta with normal sclerae, dominant form; Postmenopausal osteoporosis; Osteogenesis imperfecta, recessive perinatal lethal; Osteogenesis imperfecta type III; Ehlers-Danlos syndrome, autosomal recessive, cardiac valvular form; EHLERS-DANLOS SYNDROME, ARTHROCHALASIA TYPE, 2	2018-10-31	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana	RCV001196500	SCV001367108	pathogenic	Recurrent fractures	2019-09-09	criteria provided, single submitter	clinical testing	This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP5. This variant was detected in heterozygous state.

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