Submissions for variant NM_016599.5(MYOZ2):c.247-3C>T

gnomAD frequency: 0.00001  dbSNP: rs774202003

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000203613	SCV000259070	likely benign	not specified	2015-04-27	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000824163	SCV000965049	uncertain significance	Hypertrophic cardiomyopathy	2024-03-07	criteria provided, single submitter	clinical testing	This sequence change falls in intron 3 of the MYOZ2 gene. It does not directly change the encoded amino acid sequence of the MYOZ2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs774202003, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MYOZ2-related conditions. ClinVar contains an entry for this variant (Variation ID: 219286). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
Ambry Genetics	RCV002453734	SCV002737470	uncertain significance	Cardiovascular phenotype	2020-08-27	criteria provided, single submitter	clinical testing	The c.247-3C>T intronic variant results from a C to T substitution 3 nucleotides upstream from coding exon 3 in the MYOZ2 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003955221	SCV004767866	likely benign	MYOZ2-related disorder	2019-07-12	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).