ClinVar Miner

Submissions for variant NM_000195.5(HPS1):c.1448G>A (p.Arg483Gln)

gnomAD frequency: 0.00009  dbSNP: rs199996900
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics, Fulgent Genetics RCV002504403 SCV002816199 uncertain significance Hermansky-Pudlak syndrome 1 2021-12-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002542912 SCV003263995 uncertain significance not provided 2022-09-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 483 of the HPS1 protein (p.Arg483Gln). This variant is present in population databases (rs199996900, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with HPS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 990835). 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 HPS1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Ambry Genetics RCV002537818 SCV003683209 uncertain significance Inborn genetic diseases 2021-10-22 criteria provided, single submitter clinical testing The c.1448G>A (p.R483Q) alteration is located in exon 15 (coding exon 13) of the HPS1 gene. This alteration results from a G to A substitution at nucleotide position 1448, causing the arginine (R) at amino acid position 483 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV002542912 SCV005390021 uncertain significance not provided 2024-04-22 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001278941 SCV001465987 uncertain significance Hermansky-Pudlak syndrome 2020-04-10 no assertion criteria provided clinical testing

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