Submissions for variant NM_016599.5(MYOZ2):c.488T>C (p.Leu163Ser)

gnomAD frequency: 0.00058  dbSNP: rs143345726

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039010	SCV000062688	uncertain significance	not specified	2012-07-19	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Leu163Ser varia nt in MYOZ2 has been identified in 0.25% (11/4406) of African American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS/; dbSNP rs143345726). Computational analyses (biochemical ami no acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the normal function of the protein. While the observed frequency of this variant suggests that it is more likely to be benign, it is too low to confidently rule out a disease causing role. Additio nal information is needed to fully assess its clinical significance.
GeneDx	RCV001719756	SCV000250634	likely benign	not provided	2020-09-08	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27600940)
Ambry Genetics	RCV000246679	SCV000319133	likely benign	Cardiovascular phenotype	2019-04-16	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000459249	SCV000563521	likely benign	Hypertrophic cardiomyopathy	2024-12-17	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000515178	SCV000611484	uncertain significance	Hypertrophic cardiomyopathy 16	2017-05-23	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852986	SCV000995735	likely benign	Restrictive cardiomyopathy	2018-08-13	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798126	SCV002043499	benign	Cardiomyopathy	2019-11-07	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000515178	SCV003920262	uncertain significance	Hypertrophic cardiomyopathy 16	2021-03-30	criteria provided, single submitter	clinical testing	MYOZ2 NM_016599.4 exon 5 p.Leu163Ser (c.488T>C): This variant has been reported in the literature in one individual with HCM (Cecconi 2016 PMID:27600940). This variant is also present in 0.1% (43/24948) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/4-120085477-T-C) and is present in ClinVar, with multiple labs classifying this variant as likely benign (Variation ID:45784). However, evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.