ClinVar Miner

Submissions for variant NM_001278074.1(COL5A1):c.292G>A (p.Glu98Lys) (rs369126350)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196999 SCV000249865 uncertain significance not provided 2013-06-03 criteria provided, single submitter clinical testing p.Glu98Lys (GAG>AAG): c.292 G>A in exon 3 of the COL5A1 gene (NM_000093.3)The Glu98Lys variant in the COL5A1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Glu98Lys results in a non-conservative amino acid substitution of a negatively charged Glutamic acid with a positively charged Lysine at a position that is conserved across species. In silico analysis predicts Glu98Lys is possibly damaging to the protein structure/function. The Glu98Lys variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. Nevertheless, no mutations in nearby residues have been reported in association with Ehlers-Danlos syndrome (EDS).With the clinical and molecular information available at this time, we cannot definitively determine if Glu98Lys is a disease-causing mutation or a rare benign variant. The pathogenic role for this variant would be further supported if it occurred de novo or if it co-segregates independently with an EDS or related phenotype. This variant was found in TAAD
Invitae RCV000697085 SCV000825675 uncertain significance Ehlers-Danlos syndrome, classic type 2019-11-28 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 98 of the COL5A1 protein (p.Glu98Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs369126350, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with COL5A1-related disease. ClinVar contains an entry for this variant (Variation ID: 213008). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Fulgent Genetics,Fulgent Genetics RCV000697085 SCV000897493 uncertain significance Ehlers-Danlos syndrome, classic type 2018-10-31 criteria provided, single submitter clinical testing

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