ClinVar Miner

Submissions for variant NM_000414.4(HSD17B4):c.1537C>A (p.Pro513Thr)

dbSNP: rs764300456
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001387757 SCV001588470 pathogenic Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 2023-05-22 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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 expected to disrupt HSD17B4 protein function. ClinVar contains an entry for this variant (Variation ID: 1074454). This missense change has been observed in individual(s) with D-bifunctional protein deficiency (PMID: 24108619, 24553428). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 513 of the HSD17B4 protein (p.Pro513Thr).
Myriad Genetics, Inc. RCV001810508 SCV002060009 uncertain significance Bifunctional peroxisomal enzyme deficiency; Perrault syndrome 1 2021-11-18 criteria provided, single submitter clinical testing NM_000414.3(HSD17B4):c.1537C>A(P513T) is a missense variant classified as a variant of uncertain significance in the context of D-bifunctional protein deficiency. P513T has been observed in cases with relevant disease (PMID: 24108619). Functional assessments of this variant are not available in the literature. P513T has been observed in population frequency databases (gnomAD: EAS 0.01%). In summary, there is insufficient evidence to classify NM_000414.3(HSD17B4):c.1537C>A(P513T) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.

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