ClinVar Miner

Submissions for variant NM_000195.5(HPS1):c.1915G>A (p.Gly639Ser)

gnomAD frequency: 0.00049  dbSNP: rs116698870
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000379557 SCV000343338 uncertain significance not provided 2016-08-19 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000267888 SCV000359647 uncertain significance Hermansky-Pudlak syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000379557 SCV003263749 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 639 of the HPS1 protein (p.Gly639Ser). This variant is present in population databases (rs116698870, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with Hermansky-Pudlak syndrome and associated pulmonary fibrosis (PMID: 30985222). ClinVar contains an entry for this variant (Variation ID: 289062). 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 HPS1 protein function. 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.
PreventionGenetics, part of Exact Sciences RCV003401266 SCV004102943 uncertain significance HPS1-related condition 2023-10-03 criteria provided, single submitter clinical testing The HPS1 c.1915G>A variant is predicted to result in the amino acid substitution p.Gly639Ser. This variant was reported in an individual with Hermansky-Pudlak syndrome (Stearman. 2019. PubMed ID: 30985222). This variant is reported in 0.086% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-100177957-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas RCV003444227 SCV004171681 uncertain significance Hermansky-Pudlak syndrome 1 2023-11-24 no assertion criteria provided clinical testing

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