Submissions for variant NM_004369.4(COL6A3):c.3220G>A (p.Asp1074Asn)

gnomAD frequency: 0.00001  dbSNP: rs778403814

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000727405	SCV000618183	uncertain significance	not provided	2020-06-04	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30564623)
Eurofins Ntd Llc (ga)	RCV000727405	SCV000708269	uncertain significance	not provided	2017-05-03	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000661955	SCV000784285	uncertain significance	Ullrich congenital muscular dystrophy 1A	2018-03-05	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000661956	SCV000784286	uncertain significance	Bethlem myopathy 1A	2018-03-05	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000661957	SCV000784287	uncertain significance	Dystonia 27	2018-03-05	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000661956	SCV001230682	likely benign	Bethlem myopathy 1A	2023-08-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003278864	SCV003986081	uncertain significance	Inborn genetic diseases	2023-05-23	criteria provided, single submitter	clinical testing	The c.3220G>A (p.D1074N) alteration is located in exon 8 (coding exon 7) of the COL6A3 gene. This alteration results from a G to A substitution at nucleotide position 3220, causing the aspartic acid (D) at amino acid position 1074 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV000727405	SCV004147344	likely benign	not provided	2022-06-01	criteria provided, single submitter	clinical testing	COL6A3: BP4
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004701595	SCV005203672	uncertain significance	not specified	2024-07-05	criteria provided, single submitter	clinical testing	Variant summary: COL6A3 c.3220G>A (p.Asp1074Asn) 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 benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250242 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3220G>A in individuals affected with Ullrich Congenital Muscular Dystrophy 1C/Dystonia 27/Bethlem myopathy 1C, and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 449785). Based on the evidence outlined above, the variant was classified as uncertain significance.