ClinVar Miner

Submissions for variant NM_014365.2(HSPB8):c.266C>G (p.Pro89Arg) (rs35909818)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000362374 SCV000376632 benign Distal hereditary motor neuronopathy type 2A 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000550983 SCV000376633 likely benign Charcot-Marie-Tooth disease, type 2L 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae RCV000550983 SCV000639053 uncertain significance Charcot-Marie-Tooth disease, type 2L 2019-09-25 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 89 of the HSPB8 protein (p.Pro89Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. This variant is present in population databases (rs35909818, ExAC 0.04%), 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 HSPB8-related disease. ClinVar contains an entry for this variant (Variation ID: 307417). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Athena Diagnostics Inc RCV000992176 SCV001144233 likely benign not provided 2019-03-12 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000992176 SCV001148846 uncertain significance not provided 2017-03-01 criteria provided, single submitter clinical testing

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