Submissions for variant NM_000250.2(MPO):c.1555_1568del (p.Met519fs)

dbSNP: rs536522394

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000274466	SCV000329998	pathogenic	not provided	2016-01-26	criteria provided, single submitter	clinical testing	The c.1555_1568del14 pathogenic variant in the MPO gene has been reported previously in association with myeloperoxidase deficiency, in a father who was compound heterozygous for c.1555_1568del14 and another variant and his daughter who was heterozygous for c.1555_1568del14 and no second variant (Romano et al., 1997). The c.1555_1568del14 variant causes a frameshift starting with codon Methionine 519, changes this amino acid to a Proline residue, and creates a premature Stop codon at position 21 of the new reading frame, denoted p.Met519ProfsX21. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Functional studies show neutrophils from donors who are compound heterozygous for the c.1555_1568del14 variant and another pathogenic variant fail to form neutrophil extracellular traps (Metzler et al., 2011). The c.1555_1568del14 variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1555_1568del14 as a pathogenic variant.
CeGaT Center for Human Genetics Tuebingen	RCV000274466	SCV000575116	likely pathogenic	not provided	2017-01-31	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000003813	SCV002017534	pathogenic	Myeloperoxidase deficiency	2023-01-11	criteria provided, single submitter	clinical testing
AiLife Diagnostics, AiLife Diagnostics	RCV000274466	SCV002502244	likely pathogenic	not provided	2022-03-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003952340	SCV004770262	likely pathogenic	MPO-related condition	2024-01-05	criteria provided, single submitter	clinical testing	The MPO c.1555_1568del14 variant is predicted to result in a frameshift and premature protein termination (p.Met519Profs*21). This variant was reported as pathogenic for myeloperoxidase deficiency (Romano et al. 1997. PubMed ID: 9354683; Hou et al. 2020. PubMed ID: 31980526; Vergano et al. 2020. PubMed ID: 32758448). This variant is reported in 0.15% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in MPO are expected to be pathogenic. This variant is interpreted as likely pathogenic.
OMIM	RCV000003813	SCV000023978	pathogenic	Myeloperoxidase deficiency	2004-05-01	no assertion criteria provided	literature only