ClinVar Miner

Submissions for variant NM_000088.3(COL1A1):c.1882G>A (p.Ala628Thr) (rs113950465)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585102 SCV000692915 uncertain significance not provided 2017-10-31 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000585102 SCV000337786 uncertain significance not provided 2015-11-25 criteria provided, single submitter clinical testing
GeneDx RCV000585102 SCV000512683 uncertain significance not provided 2018-10-26 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL1A1 gene. The A628T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A628T 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 where only amino acids with similar properties to Alanine are tolerated across species. The A628T variant is located in the Gly-Xaa-Yaa triple helical region of the pro-alpha1(I) chain encoded by the COL1A1 gene. However, while triplet glycine substitutions are the most common cause of osteogenesis imperfecta (OI), the effect of missense substitution at the X and Y positions are more difficult to predict. In addition, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, the Exome Aggregation Consortium (ExAC) and the 1000 Genomes Project reports A628T was observed in 5/11,578 alleles from individuals of Latino background and 2/694 alleles from individuals of Ad Mixed American background, respectively.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
GenomeConnect, ClinGen RCV000029561 SCV000607232 not provided Osteogenesis imperfecta no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Integrated Genetics/Laboratory Corporation of America RCV000029561 SCV000052213 uncertain Osteogenesis imperfecta 2011-08-18 criteria provided, single submitter curation Converted during submission to Uncertain significance.
Invitae RCV000532108 SCV000627191 likely benign Osteogenesis imperfecta type I 2017-09-18 criteria provided, single submitter clinical testing

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