ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.3818A>G (p.Lys1273Arg) (rs144614075)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000725829 SCV000233388 uncertain significance not provided 2018-03-21 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL3A1 gene. The K1273R variant has been reported previously in one individual with vascular Ehlers-Danlos syndrome (vEDS) and in two unrelated patients with arterial aneurysms (Ong et al., 2010; Frank et al., 2015). K1273R was also reported as a variant of uncertain significance in a patient with familial thoracic aortic aneurysm (TAA) (Schubert et al., 2016). This variant has been observed in 10/65,996 (0.01%) Non-Finnish European alleles in the Exome Aggregation Consortium data-set (Lek et al., 2016). Additionally, the K1273R variant has been seen in multiple individuals referred for Marfan/TAAD testing at GeneDx; however, segregation data is limited thus far due to insufficient participation by informative family members.The K1273R variant 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 not conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Notably, the K1273R variant does not affect a Glycine residue in a Gly-X-Y motif in the triple helical region of the COL3A1 gene, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012).
Invitae RCV001087510 SCV000262437 likely benign Ehlers-Danlos syndrome, type 4 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000244720 SCV000319224 likely benign Cardiovascular phenotype 2020-07-17 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000725829 SCV000339677 uncertain significance not provided 2016-03-03 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000515270 SCV000611385 uncertain significance Ehlers-Danlos syndrome, type 4; Ehlers-Danlos syndrome, type 3 2017-05-23 criteria provided, single submitter clinical testing
Color Health, Inc RCV000771822 SCV000904527 likely benign Familial thoracic aortic aneurysm and aortic dissection 2019-10-08 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001087510 SCV001299204 benign Ehlers-Danlos syndrome, type 4 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Johns Hopkins Genomics, Johns Hopkins University RCV000725829 SCV001762374 likely benign not provided 2021-07-02 criteria provided, single submitter clinical testing

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