ClinVar Miner

Submissions for variant NM_002156.5(HSPD1):c.551A>G (p.Asn184Ser)

gnomAD frequency: 0.00035  dbSNP: rs67967266
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Unit for Genetic & Epidemiological Research on Neurological Disorders, Instituto de Investigação e Inovação em Saúde RCV000515926 SCV000574472 uncertain significance Hereditary spastic paraplegia 2017-03-07 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001326732 SCV001517774 uncertain significance Spastic paraplegia 2024-01-25 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 184 of the HSPD1 protein (p.Asn184Ser). This variant is present in population databases (rs67967266, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of hereditary spastic paraplegia (PMID: 28832565). ClinVar contains an entry for this variant (Variation ID: 424666). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt HSPD1 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect HSPD1 function (PMID: 27630992). 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV000515926 SCV002104759 uncertain significance Hereditary spastic paraplegia 2020-03-01 criteria provided, single submitter clinical testing

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