ClinVar Miner

Submissions for variant NM_001540.5(HSPB1):c.248_249delinsAT (p.Ser83Asn) (rs1563651975)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757373 SCV000885570 uncertain significance not provided 2018-01-22 criteria provided, single submitter clinical testing The HSBP1 c.248_249delGCinsAT; p.Ser83Asn variant, to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is absent from the general population databases (1000 Genomes Project, Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The serine at position 83 is highly conserved, considering 12 species, and computational analyses of the effects of the p.Ser83Asn variant on protein structure and function make conflicting predictions (SIFT: tolerated, MutationTaster: disease causing, PolyPhen-2:benign). Based on the available information, the clinical significance of the p.Ser83Asn variant cannot be determined with certainty.
Athena Diagnostics Inc RCV000757373 SCV001144217 uncertain significance not provided 2019-02-18 criteria provided, single submitter clinical testing
Invitae RCV001224694 SCV001396909 uncertain significance Charcot-Marie-Tooth disease axonal type 2F 2019-06-18 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 83 of the HSPB1 protein (p.Ser83Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals with HSPB1-related conditions. ClinVar contains an entry for this variant (Variation ID: 618680). 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.

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