Submissions for variant NM_000088.4(COL1A1):c.3061G>C (p.Glu1021Gln)

gnomAD frequency: 0.00014  dbSNP: rs139593707

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000631488	SCV000752570	likely benign	Osteogenesis imperfecta type I	2024-12-27	criteria provided, single submitter	clinical testing
GeneDx	RCV001566557	SCV001790096	uncertain significance	not provided	2024-07-01	criteria provided, single submitter	clinical testing	Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease (HGMD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002279450	SCV002564715	uncertain significance	Osteogenesis imperfecta	2020-02-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002279451	SCV002565506	uncertain significance	Ehlers-Danlos syndrome	2021-11-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002448936	SCV002752976	uncertain significance	Cardiovascular phenotype	2024-10-18	criteria provided, single submitter	clinical testing	The p.E1021Q variant (also known as c.3061G>C), located in coding exon 42 of the COL1A1 gene, results from a G to C substitution at nucleotide position 3061. The glutamic acid at codon 1021 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GenomeConnect - Invitae Patient Insights Network	RCV003330848	SCV004037531	not provided	Infantile cortical hyperostosis; Osteogenesis imperfecta; Ehlers-danlos syndrome, arthrochalasia type, 2		no assertion provided	phenotyping only	Variant classified as Likely benign and reported on 02-18-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.
PreventionGenetics, part of Exact Sciences	RCV004737908	SCV005360567	uncertain significance	COL1A1-related disorder	2024-08-23	no assertion criteria provided	clinical testing	The COL1A1 c.3061G>C variant is predicted to result in the amino acid substitution p.Glu1021Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.032% of alleles in individuals of European (Non-Finnish) descent in gnomAD, which is more frequent than expected for a disease-causing variant in COL1A1. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.