Submissions for variant NM_000195.5(HPS1):c.122C>T (p.Pro41Leu)

gnomAD frequency: 0.00068  dbSNP: rs142934882

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000380587	SCV000359678	uncertain significance	Hermansky-Pudlak syndrome 1	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 (formerly Invitae), Labcorp	RCV002059510	SCV002342890	likely benign	not provided	2025-01-23	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000380587	SCV003808763	uncertain significance	Hermansky-Pudlak syndrome 1	2019-04-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004021459	SCV004882580	uncertain significance	Inborn genetic diseases	2024-03-05	criteria provided, single submitter	clinical testing	The c.122C>T (p.P41L) alteration is located in exon 4 (coding exon 2) of the HPS1 gene. This alteration results from a C to T substitution at nucleotide position 122, causing the proline (P) at amino acid position 41 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003920216	SCV004737246	likely benign	HPS1-related disorder	2022-04-19	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).