Submissions for variant NM_000121.4(EPOR):c.1462C>T (p.Pro488Ser)

gnomAD frequency: 0.00541  dbSNP: rs142094773

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000258855	SCV000410629	likely benign	Primary familial polycythemia due to EPO receptor mutation	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000953082	SCV001099632	benign	not provided	2023-12-18	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001258311	SCV001435260	benign	Intellectual disability-hypotonic facies syndrome, X-linked, 1		criteria provided, single submitter	research	The heterozygous p.Pro488Ser variant in EPOR has been identified in an individual with polycythaemia (PMID: 8174675), and has been identified in >3% of Latino chromosomes and 13 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In vitro functional studies provide some evidence that the p.Pro488Ser variant may not impact protein function (PMID: 8174675). However, these types of assays may not accurately represent biological function. In summary, this variant meets criteria to be classified as benign for autosomal dominant polycythaemia.
CeGaT Center for Human Genetics Tuebingen	RCV000953082	SCV004137863	benign	not provided	2022-09-01	criteria provided, single submitter	clinical testing	EPOR: BP4, BS1, BS2
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000258855	SCV004562903	likely benign	Primary familial polycythemia due to EPO receptor mutation	2023-11-30	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000953082	SCV005209449	likely benign	not provided		criteria provided, single submitter	not provided
GeneReviews	RCV000258855	SCV000328591	not provided	Primary familial polycythemia due to EPO receptor mutation		no assertion provided	literature only