ClinVar Miner

Submissions for variant NM_000088.3(COL1A1):c.3233T>C (p.Val1078Ala) (rs767525556)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000259210 SCV000404122 uncertain significance Osteogenesis imperfecta 2018-01-13 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000319126 SCV000404123 likely benign Ehlers-Danlos syndrome, procollagen proteinase deficient 2018-01-13 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 Clinical Services Laboratory,Illumina RCV000355446 SCV000404124 uncertain significance Infantile cortical hyperostosis 2018-01-13 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000521091 SCV000621444 uncertain significance not provided 2018-04-25 criteria provided, single submitter clinical testing The V1078A variant of uncertain significance in the COL1A1 gene has not been published as pathogenic or benign to our knowledge. This variant has been identified in conjunction with additional cardiogenetic variants in individuals with features of HDCT or referred for HDCT genetic testing at GeneDx. However, thus far, segregation data is limited for these individuals due to the lack of clinical information provided and insufficient participation by informative family members. In addition, V1078A is observed in 24/89,634 alleles (0.03%) from individuals of European (non-Finnish) background in large population cohorts (Lek et al., 2016). The V1078A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Furthermore, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Finally, V1078A does not affect a glycine residue in a Gly-X-Y motif in the triple helical region of the COL1A1, where the majority of pathogenic missense variants occur (Stenson et al., 2014).
Invitae RCV000695671 SCV000824185 likely benign Osteogenesis imperfecta type I 2019-12-19 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765369 SCV000896634 uncertain significance Osteogenesis imperfecta with normal sclerae, dominant form; Postmenopausal osteoporosis; Osteogenesis imperfecta, recessive perinatal lethal; Osteogenesis imperfecta type III; Infantile cortical hyperostosis; Ehlers-Danlos syndrome, procollagen proteinase deficient; Osteogenesis imperfecta type I 2018-10-31 criteria provided, single submitter clinical testing

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