Submissions for variant NM_000089.4(COL1A2):c.3853A>C (p.Asn1285His)

gnomAD frequency: 0.00057  dbSNP: rs144797861

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413044	SCV000491755	uncertain significance	not specified	2016-11-17	criteria provided, single submitter	clinical testing	The N1285H variant in the COL1A2 gene has published as a variant of uncertain significance in a patient with OI who also harbored a known pathogenic variant in a different gene (Pollitt et al., 2006). Although not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports N1285H was observed in 10/8600 alleles (0.12%) from individuals of European background, indicating it may be a rare variant in this population. The N1285H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. However, in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret N1285H as a variant of uncertain significance.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. This result cannot be interpreted for diagnosis or used for family member screening at this time.
Invitae	RCV002230749	SCV000627345	likely benign	Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1	2024-01-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000585259	SCV000693242	uncertain significance	not provided	2018-11-01	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000585259	SCV000862643	uncertain significance	not provided	2018-08-14	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000764737	SCV000895872	uncertain significance	Osteogenesis imperfecta with normal sclerae, dominant form; Postmenopausal osteoporosis; Osteogenesis imperfecta, perinatal lethal; Osteogenesis imperfecta type III; Ehlers-Danlos syndrome, cardiac valvular type; Ehlers-danlos syndrome, arthrochalasia type, 2	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001164957	SCV001327120	likely benign	Osteogenesis imperfecta	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001164958	SCV001327121	benign	Ehlers-danlos syndrome, arthrochalasia type, 2	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000585259	SCV001477543	likely benign	not provided	2020-04-16	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001164957	SCV002564796	uncertain significance	Osteogenesis imperfecta	2021-03-02	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002278645	SCV002565586	uncertain significance	Ehlers-Danlos syndrome	2021-03-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002356509	SCV002619945	likely benign	Cardiovascular phenotype	2019-11-11	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.