Submissions for variant NM_004370.6(COL12A1):c.1471G>C (p.Glu491Gln)

gnomAD frequency: 0.00016  dbSNP: rs367630003

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000695719	SCV000824234	likely benign	Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2	2024-01-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001592886	SCV001814770	uncertain significance	not provided	2022-07-25	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 26582918)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002271569	SCV002555624	uncertain significance	not specified	2022-06-03	criteria provided, single submitter	clinical testing	Variant summary: COL12A1 c.1471G>C (p.Glu491Gln) results in a conservative amino acid change located in the von Willebrand factor, type A (IPR002035) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7.2e-05 in 249078 control chromosomes. This frequency does not allow conclusions about variant significance. To our knowledge, no occurrence of c.1471G>C in individuals affected with Bethlem Myopathy 2/COL12A1-related disorders and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Revvity Omics, Revvity	RCV001592886	SCV003832832	uncertain significance	not provided	2022-11-15	criteria provided, single submitter	clinical testing
GenomeConnect - Invitae Patient Insights Network	RCV000695719	SCV001749351	not provided	Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 08-08-2018 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.