ClinVar Miner

Submissions for variant NM_000432.4(MYL2):c.402+1G>T

dbSNP: rs1555257746
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000579194 SCV000681170 uncertain significance not provided 2017-12-04 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYL2 gene. The c.402+1 G>T variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016). The c.402+1 G>T variant is predicted to destroy the canonical splice donor site in intron 6 and to cause abnormal gene splicing. However, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined. In addition, only a few other splice site variants in the MYL2 gene have been reported in HGMD in association with HCM, and the majority of variants reported in this gene are missense variants (Stenson et al., 2014).
Labcorp Genetics (formerly Invitae), Labcorp RCV001860014 SCV002171819 uncertain significance Hypertrophic cardiomyopathy 10 2022-07-05 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the MYL2 gene. It does not directly change the encoded amino acid sequence of the MYL2 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYL2-related conditions. ClinVar contains an entry for this variant (Variation ID: 489183). 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 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.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV001860014 SCV005438569 uncertain significance Hypertrophic cardiomyopathy 10 2024-12-18 criteria provided, single submitter clinical testing

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