Submissions for variant NM_024747.6(HPS6):c.1732C>T (p.Arg578Ter)

dbSNP: rs940319528

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003660889	SCV004375973	pathogenic	not provided	2023-01-24	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 996367). This premature translational stop signal has been observed in individual(s) with Hermansky–Pudlak syndrome (PMID: 33878481). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg578*) in the HPS6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 198 amino acid(s) of the HPS6 protein. This variant disrupts a region of the HPS6 protein in which other variant(s) (p.Gln680*) have been determined to be pathogenic (PMID: 27225848). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001290774	SCV001478885	likely pathogenic	Hermansky-Pudlak syndrome 6	2020-11-13	no assertion criteria provided	clinical testing