Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001106566 | SCV001263642 | uncertain significance | Hermansky-Pudlak syndrome 6 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV001856429 | SCV002150286 | uncertain significance | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 449 of the HPS6 protein (p.Ser449Cys). This variant is present in population databases (rs141068948, gnomAD 0.03%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with HPS6-related conditions. ClinVar contains an entry for this variant (Variation ID: 879248). 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 HPS6 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. |
| Fulgent Genetics, |
RCV001106566 | SCV002784919 | uncertain significance | Hermansky-Pudlak syndrome 6 | 2022-04-26 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002556087 | SCV003691999 | uncertain significance | Inborn genetic diseases | 2022-08-31 | criteria provided, single submitter | clinical testing | The c.1346C>G (p.S449C) alteration is located in exon 1 (coding exon 1) of the HPS6 gene. This alteration results from a C to G substitution at nucleotide position 1346, causing the serine (S) at amino acid position 449 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Prevention |
RCV004751882 | SCV005346095 | uncertain significance | HPS6-related disorder | 2024-04-30 | no assertion criteria provided | clinical testing | The HPS6 c.1346C>G variant is predicted to result in the amino acid substitution p.Ser449Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.029% of alleles in individuals of European (Non-Finnish) descent in gnomAD, including one homozygote. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |