ClinVar Miner

Submissions for variant NM_080679.2(COL11A2):c.4331G>A (p.Arg1444Gln) (rs145343609)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724415 SCV000231896 uncertain significance not provided 2017-10-13 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000218581 SCV000271605 uncertain significance not specified 2017-03-20 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Arg1551Gln va riant in COL11A2 has been reported by our laboratory in one individual with hear ing loss. It has also been reported in ClinVar (Variation ID# 198337) as likely benign or of uncertain significance. This variant has been identified in 0.1% (6 7/66340) of European chromosomes by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org; dbSNP rs145343609). Although this variant has been s een in the general population, its frequency is not high enough to rule out a pa thogenic role. Arginine (Arg) at position 1551 is not conserved in 1 mammal (ten rec) or evolutionarily distant species, supporting that a change at this positio n may be tolerated. Computational prediction tools do not provide strong support for or against an impact to the protein; however, splice prediction tools do su ggest an impact to splicing. In summary, while the clinical significance of the p.Arg1551Gln variant is uncertain, the frequency and conservation data suggest i t is more likely to be benign.
Illumina Clinical Services Laboratory,Illumina RCV000320721 SCV000462251 likely benign Stickler Syndrome, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000377623 SCV000462252 likely benign Fibrochondrogenesis 1 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000290184 SCV000462253 likely benign Nonsyndromic Hearing Loss, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000328722 SCV000462254 likely benign Otospondylomegaepiphyseal dysplasia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000381022 SCV000462255 likely benign Weissenbacher-Zweymuller syndrome 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000724415 SCV000573635 uncertain significance not provided 2018-07-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL11A2 gene. The R1551Q variant has not been published as pathogenic or been reported as benign to our knowledge. The R1151Q variant is observed at a frequency of 130/126324 alleles (0.1%) in individuals of European (non-Finnish) background in large population cohorts (Lek et al., 2016). Additionally, R1151Q has been reported as a variant of uncertain significance by other laboratories in ClinVar (SCV000231896.3, SCV000271605.1, Landrum et al., 2016). The R1551Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Furthermore, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function.

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