ClinVar Miner

Submissions for variant NM_001278074.1(COL5A1):c.3260G>C (p.Gly1087Ala) (rs559882772)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000488963 SCV000576726 uncertain significance not provided 2017-11-06 criteria provided, single submitter clinical testing The G1087A variant of uncertain significance in the COL5A1 gene has not been published as pathogenic or been reported as benign to our knowledge. G1087A is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is generally conserved across species, yet A1087 is the wild-type residue in at least one species. Nevertheless, in silico analysis predicts this variant is probably damaging to the protein structure/function. The G1087A variant affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL5A1 gene, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012). However, there is also a Gly substitution (G530S) within a Gly-X-Y motif in the COL5A1 gene which does not have a clear pathogenic effect (Symoens et al., 2012), illustrating that the clinical significance of Gly substitutions in the collagen genes can vary. In addition, G1087A was observed in 53/7,914 (0.7%) alleles in individuals of South Asian ancestry in the Exome Aggregation Consortium, indicating it may be a rare benign variant in this population (Lek et al., 2016). Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000767943 SCV000898629 uncertain significance Ehlers-Danlos syndrome, classic type 2017-12-22 criteria provided, single submitter clinical testing COL5A1 NM_000093.4 exon 42 p.Gly1087Ala (c.3260G>C): This variant has not been reported in the literature but is present in 0.7% (170/22822) of South Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs559882772). This variant is present in ClinVar (Variation ID: 426317). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Invitae RCV000767943 SCV001008189 benign Ehlers-Danlos syndrome, classic type 2019-12-31 criteria provided, single submitter clinical testing

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