ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.3220G>A (p.Asp1074Asn) (rs778403814)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000727405 SCV000618183 uncertain significance not provided 2018-10-11 criteria provided, single submitter clinical testing The D1074N variant in the COL6A3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D1074N variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The D1074N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret D1074N as a variant of uncertain significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics 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 1 2018-03-05 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000661956 SCV000784286 uncertain significance Bethlem myopathy 1 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
Invitae RCV000661956 SCV001230682 uncertain significance Bethlem myopathy 1 2019-04-16 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 1074 of the COL6A3 protein (p.Asp1074Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs778403814, ExAC 0.002%). This variant has not been reported in the literature in individuals with COL6A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 449785). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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