ClinVar Miner

Submissions for variant NM_001540.5(HSPB1):c.610G>A (p.Ala204Thr) (rs367857772)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000198307 SCV000254742 uncertain significance Charcot-Marie-Tooth disease axonal type 2F 2020-01-06 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 204 of the HSPB1 protein (p.Ala204Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs367857772, ExAC 0.03%), 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 an HSPB1-related disease. ClinVar contains an entry for this variant (Variation ID: 216545). 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, this variant has uncertain impact on HSPB1 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000765975 SCV000897397 uncertain significance Charcot-Marie-Tooth disease axonal type 2F; Distal hereditary motor neuronopathy type 2B 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001159593 SCV001321316 benign Distal hereditary motor neuronopathy type 2B 2017-07-24 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Clinical Services Laboratory,Illumina RCV000198307 SCV001321317 uncertain significance Charcot-Marie-Tooth disease axonal type 2F 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Molecular Genetics Laboratory,London Health Sciences Centre RCV001174181 SCV001337307 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing

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