Submissions for variant NM_032578.4(MYPN):c.3103A>G (p.Met1035Val)

gnomAD frequency: 0.00007  dbSNP: rs201975081

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001704650	SCV000589449	likely benign	not provided	2021-06-04	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27535533, 26582918)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000555234	SCV000659200	uncertain significance	Dilated cardiomyopathy 1KK	2024-01-17	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1035 of the MYPN protein (p.Met1035Val). This variant is present in population databases (rs201975081, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with MYPN-related conditions. ClinVar contains an entry for this variant (Variation ID: 431886). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics	RCV000764910	SCV000896072	uncertain significance	Dilated cardiomyopathy 1KK; MYPN-related myopathy	2018-10-31	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852612	SCV000995315	likely benign	Cardiomyopathy	2018-06-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002323861	SCV002607805	likely benign	Cardiovascular phenotype	2020-08-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity	RCV001704650	SCV003810979	uncertain significance	not provided	2020-03-09	criteria provided, single submitter	clinical testing
Clinical Genomics Laboratory, Stanford Medicine	RCV000555234	SCV005051689	uncertain significance	Dilated cardiomyopathy 1KK	2021-07-21	criteria provided, single submitter	clinical testing	The p.Met1035Val variant in the MYPNgene has not been previously reported in association with disease. This variant has been identified in 57/35,428 Latino/Admixed American chromosomes (58/282,820 chromosomes overall) by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). This population frequency is likely too high to be consistent with autosomal dominant disease, but is low enough to be consistent with a recessive carrier frequency. Computational tools do not predict that the p.Met1035Val variant impacts protein function; however, the accuracy of in silicoalgorithms is limited. These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of the p.Met1035Valvariant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: BS1_Supporting]