ClinVar Miner

Submissions for variant NM_000089.3(COL1A2):c.286A>G (p.Met96Val) (rs763509640)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc RCV000659367 SCV000781178 uncertain significance Connective tissue disorder 2016-11-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764734 SCV000895869 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 RCV000486132 SCV000573481 uncertain significance not specified 2017-02-17 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL1A2 gene. The M96V variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). However, the M96V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Furthermore, this substitution occurs at a position that is only conserved through mammals and in silico analysis suggests that this variant likely does not alter the protein structure/function.
Invitae RCV000542304 SCV000627329 uncertain significance Ehlers-Danlos syndrome, classic type; Osteogenesis imperfecta type I 2017-12-26 criteria provided, single submitter clinical testing This sequence change replaces methionine with valine at codon 96 of the COL1A2 protein (p.Met96Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is present in population databases (rs763509640, ExAC 0.006%). This variant has not been reported in the literature in individuals with a COL1A2-related disease. ClinVar contains an entry for this variant (Variation ID: 423747). 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: "Unknown"; Align-GVGD: "Class C15"). In summary, this variant has uncertain impact on COL1A2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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