ClinVar Miner

Submissions for variant NM_080679.2(COL11A2):c.4174G>A (p.Glu1392Lys) (rs727504543)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000155698 SCV000205408 uncertain significance not specified 2013-06-11 criteria provided, single submitter clinical testing The Glu1499Lys variant in COL11A2 has not been reported in individuals with hear ing loss or in large population studies. Computational analyses (biochemical ami no acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. In summary, additional data is needed to determine the clinical significance of this variant.
GeneDx RCV000766448 SCV000573705 uncertain significance not provided 2017-02-24 criteria provided, single submitter clinical testing The c.4495 G>A variant in the COL11A2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.4495 G>A variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In-silico splice prediction models predict that c.4495 G>A may create or strengthen a cryptic splice donor site in exon 63 that could supplant the natural splice acceptor site. However, in the absence of RNA/functional studies, the actual effect of the c.4495 G>A change in this individual is unknown. If c.3985G>T does not alter splicing, it will result in the E1499K missense change. The E1499K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret c.4495 G>A as a variant of uncertain significance.
GenomeConnect, ClinGen RCV000845018 SCV000986851 not provided COL11A2- Related Disorder no assertion provided phenotyping only Variant interpretted as Uncertain significance and reported on 02/28/2017 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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