ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.1188C>T (p.Gly396=) (rs745743884)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000757115 SCV000618907 uncertain significance not provided 2017-07-10 criteria provided, single submitter clinical testing The c.1188 C>T (G396=) variant of uncertain significance in the COL3A1 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant was observed in 3/16,430 (0.02%) alleles from individuals of South Asian ancestry in the Exome Aggregation Consortium (Lek et al., 2016). The c.1188 C>T substitution occurs at a nucleotide position that is not conserved, as thymine (T) is the wild-type nucleotide in multiple species. In silico splicing algorithms predict this variant may create a cryptic splice donor site upstream of the natural splice donor site in intron 17 of the COL3A1 gene; however, in the absence of functional mRNA studies, the physiological consequence of this variant on splicing cannot be precisely determined.
Ambry Genetics RCV000618454 SCV000738516 likely benign Cardiovascular phenotype 2017-03-02 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757115 SCV000885234 uncertain significance not provided 2018-02-20 criteria provided, single submitter clinical testing The COL3A1 c.1188C>T; p.Gly396Gly variant (rs745743884; ClinVar variant ID 450335), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This synonymous variant is in a weakly conserved nucleotide, but computational analyses predict that this variant may impact splicing by creating a novel cryptic donor site (Alamut v.2.10); however, no functional studies have been performed to confirm or refute this prediction. This variant is listed in the genome Aggregation Database (gnomAD) with a South Asian population frequency of 0.04% (identified on 12 out of 30,780 chromosomes). Based on the available information, the clinical significance of the c.1188C>T cannot be determined with certainty.
Color Health, Inc RCV000777601 SCV000913467 likely benign Familial thoracic aortic aneurysm and aortic dissection 2018-08-02 criteria provided, single submitter clinical testing
Invitae RCV001078840 SCV001014673 likely benign Ehlers-Danlos syndrome, type 4 2020-06-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000757115 SCV001153219 likely benign not provided 2017-05-01 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000777601 SCV001333512 likely benign Familial thoracic aortic aneurysm and aortic dissection 2018-02-01 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001078840 SCV001468336 uncertain significance Ehlers-Danlos syndrome, type 4 2020-06-04 criteria provided, single submitter clinical testing COL3A1 NM_ 000090.3 exon 17 p.Gly396= (c.1188C>T): This variant has not been reported in the literature but is present in 0.03% (12/30612) of South Asian alleles in the Genome Aggregation Database ( This variant is present in ClinVar (Variation ID:450335). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Splice prediction tools suggest that this variant may affect splicing by creating a cryptic donor splice site. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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