ClinVar Miner

Submissions for variant NM_001540.5(HSPB1):c.383A>G (p.Gln128Arg) (rs558882005)

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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 RCV000705379 SCV000470064 likely benign Charcot-Marie-Tooth disease axonal type 2F 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.
Illumina Clinical Services Laboratory,Illumina RCV000678497 SCV000470065 benign Distal hereditary motor neuronopathy type 2B 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.
Biochimie - Maladies Neurologiques Hereditaires,Hospices Civils de Lyon RCV000678497 SCV000804564 likely pathogenic Distal hereditary motor neuronopathy type 2B 2017-02-02 criteria provided, single submitter clinical testing
Invitae RCV000705379 SCV000834372 uncertain significance Charcot-Marie-Tooth disease axonal type 2F 2019-12-13 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 128 of the HSPB1 protein (p.Gln128Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs558882005, ExAC 0.02%). This variant has been observed in an individual with distal hereditary motor neuropathy (PMID: 28144995). ClinVar contains an entry for this variant (Variation ID: 360738). Experimental studies have shown that this missense change causes hyperphosphorylation of neurofilaments in vitro (PMID: 28144995). 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.
Molecular Genetics Laboratory,London Health Sciences Centre RCV001172549 SCV001335610 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing

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