ClinVar Miner

Submissions for variant NM_000195.5(HPS1):c.1189del (p.Gln397fs) (rs281865084)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000020181 SCV000359659 likely pathogenic Hermansky-Pudlak syndrome 1 2017-04-27 criteria provided, single submitter clinical testing The HPS1 c.1189delC (p.Gln397SerfsTer2) variant results in a frameshift and is predicted to cause a premature termination of the protein. The variant is reported in six studies in which it is found in a total of nine out of 43 individuals with Hermansky-Pudlak syndrome (HPS), including two homozygotes, one hemizygote, and six compound heterozygotes, and in four unaffected heterozygous family members (Oh et al. 1998; Shotelersuk et al. 1998; Griffin et al. 2005; Huizing et al. 2007; Sandrock et al. 2010; Westmoreland et al. 2016). Control data are unavailable for this variant, which is reported at a frequency of 0.00012 in the European (non-Finnish) population of the Exome Aggregation Consortium. Northern blot analysis of fibroblasts from the hemizygous individual showed significantly reduced HPS RNA (Shotelersuk et al. 1998). Based on the collective evidence, the p.Gln397SerfsTer2 variant is classified as pathogenic for Hermansky-Pudlak syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000851664 SCV000899448 pathogenic Hermansky-Pudlak syndrome 2019-02-01 criteria provided, single submitter research
Invitae RCV000796076 SCV000935571 pathogenic not provided 2018-08-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln397Serfs*2) in the HPS1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs281865084, ExAC 0.01%). This variant has been observed in several individuals affected with HPS1-related conditions (PMID: 9497254, 20514622, 28081892). This variant is also known as E397delC in the literature. ClinVar contains an entry for this variant (Variation ID: 21091). Loss-of-function variants in HPS1 are known to be pathogenic (PMID: 12442288, 16185271). For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000020181 SCV000040514 pathologic Hermansky-Pudlak syndrome 1 2012-10-11 no assertion criteria provided curation Converted during submission to Pathogenic.

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