ClinVar Miner

Submissions for variant NM_016599.5(MYOZ2):c.302C>A (p.Ser101Ter)

dbSNP: rs138061447
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000172063 SCV000051018 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
GeneDx RCV000172063 SCV000250632 uncertain significance not provided 2014-04-15 criteria provided, single submitter clinical testing p.Ser101Stop (TCG>TAG): c.302 C>A in exon 4 of the MYOZ2 gene (NM_016599.4). A variant of unknown significance has been identified in the MYOZ2 gene. The S101X 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. S101X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. However, the S101X sequence change in the MYOZ2 gene was reported as a variant of unknown significance (Ng et al., 2013). S101X was reported in one individual from 870 participants not selected for a clinical phenotype or family history of arrhythmia or cardiomyopathy, who underwent whole exome sequencing as part of the ClinSeq study (Ng et al., 2013). The authors piloted a method to identify incidental results in cardiomyopathy and arrhythmia-associated alleles and provided interpretation for these variants (Ng et al., 2013). The S101X variant was classified as a variant of unknown significance given that no loss-of-function mutations have been reported in the MYOZ2 gene in association with cardiomyopathy (Ng et al., 2013).Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in CARDIOMYOPATHY
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798610 SCV002043498 uncertain significance Cardiomyopathy 2020-05-25 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001852093 SCV002154370 uncertain significance Hypertrophic cardiomyopathy 2024-12-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser101*) in the MYOZ2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MYOZ2 cause disease. This variant is present in population databases (rs138061447, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with left ventricular hypertrophy (PMID: 31534214). ClinVar contains an entry for this variant (Variation ID: 191742). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
AiLife Diagnostics, AiLife Diagnostics RCV000172063 SCV002502307 uncertain significance not provided 2021-09-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002433748 SCV002753424 uncertain significance Cardiovascular phenotype 2024-09-10 criteria provided, single submitter clinical testing The p.S101* variant (also known as c.302C>A), located in coding exon 3 of the MYOZ2 gene, results from a C to A substitution at nucleotide position 302. This changes the amino acid from a serine to a stop codon within coding exon 3. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of MYOZ2 has not been clearly established as a mechanism of disease. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Fulgent Genetics, Fulgent Genetics RCV002485100 SCV002788363 uncertain significance Hypertrophic cardiomyopathy 16 2021-10-20 criteria provided, single submitter clinical testing

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