Submissions for variant NM_000194.2(HPRT1):c.151C>T (p.Arg51Ter)

dbSNP: rs137852494

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000153366	SCV000202850	pathogenic	not provided	2013-12-02	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000010761	SCV000923596	pathogenic	Lesch-Nyhan syndrome	2019-01-01	criteria provided, single submitter	clinical testing
Invitae	RCV001224361	SCV001396551	pathogenic	Partial hypoxanthine-guanine phosphoribosyltransferase deficiency; Lesch-Nyhan syndrome	2023-04-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 10060). This premature translational stop signal has been observed in individuals with Lesch-Nyhan disease (PMID: 17027311, 25481104). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg51*) in the HPRT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HPRT1 are known to be pathogenic (PMID: 15571220, 17027311, 22157001).
3billion	RCV000010761	SCV002012265	pathogenic	Lesch-Nyhan syndrome	2021-10-02	criteria provided, single submitter	clinical testing	Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant has been reported as pathogenic (ClinVar ID: VCV000010060.7). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx	RCV000153366	SCV004170501	pathogenic	not provided	2023-10-25	criteria provided, single submitter	clinical testing	Identified in multiple unrelated patients with clinical features consistent with Lesch-Nyhan syndrome in published literature (Oh et al., 2011; Fu et al., 2015; Cho et al., 2019; Madeo et al., 2019); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21331772, 25525159, 25481104, 2323782, 8946118, 31624056, 16336979, 31129767, 31182398, 33584783, 35559039)
OMIM	RCV000010761	SCV000030987	pathogenic	Lesch-Nyhan syndrome	1990-04-01	no assertion criteria provided	literature only
OMIM	RCV000010762	SCV000030988	other	HPRT FUJIMI	2011-05-12	no assertion criteria provided	literature only
Department of Pediatrics, Samsung Medical Center, Samsung Medical Center	RCV001252944	SCV001164087	uncertain significance	Microcephaly		no assertion criteria provided	research