ClinVar Miner

Submissions for variant NM_000089.3(COL1A2):c.3853A>C (p.Asn1285His) (rs144797861)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585259 SCV000693242 uncertain significance not provided 2017-10-31 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics 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, 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
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 RCV000559417 SCV000627345 uncertain significance Ehlers-Danlos syndrome, classic type; Osteogenesis imperfecta type I 2018-05-14 criteria provided, single submitter clinical testing This sequence change replaces asparagine with histidine at codon 1285 of the COL1A2 protein (p.Asn1285His). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and histidine. This variant is present in population databases (rs144797861, ExAC 0.07%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in an individual with osteogenesis imperfecta (PMID: 16786509). However, in that individual a pathogenic allele was also identified in COL1A1, which suggests that this c.3853A>C variant was not the primary cause of disease. ClinVar contains an entry for this variant (Variation ID: 373178). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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