ClinVar Miner

Submissions for variant NM_000195.5(HPS1):c.866C>T (p.Thr289Met)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003073774 SCV003448224 uncertain significance not provided 2021-09-17 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 289 of the HPS1 protein (p.Thr289Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs200119414, ExAC 0.01%). This variant has not been reported in the literature in individuals with HPS1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV003060193 SCV003605845 uncertain significance Inborn genetic diseases 2022-03-29 criteria provided, single submitter clinical testing The c.866C>T (p.T289M) alteration is located in exon 9 (coding exon 7) of the HPS1 gene. This alteration results from a C to T substitution at nucleotide position 866, causing the threonine (T) at amino acid position 289 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005034617 SCV005665022 uncertain significance Hermansky-Pudlak syndrome 1 2024-04-02 criteria provided, single submitter clinical testing

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