ClinVar Miner

Submissions for variant NM_017534.6(MYH2):c.4537+1G>A

gnomAD frequency: 0.00001  dbSNP: rs567336764
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001330753 SCV001522541 likely pathogenic Myopathy, proximal, and ophthalmoplegia 2020-02-06 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Revvity Omics, Revvity RCV001330753 SCV002017663 pathogenic Myopathy, proximal, and ophthalmoplegia 2019-12-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001330753 SCV003475327 likely pathogenic Myopathy, proximal, and ophthalmoplegia 2024-11-11 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 32 of the MYH2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MYH2 are known to be pathogenic (PMID: 20418530, 23388406, 24193343). This variant is present in population databases (rs567336764, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with MYH2-related conditions (PMID: 33250842). ClinVar contains an entry for this variant (Variation ID: 1029470). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV003433116 SCV004141991 likely pathogenic not provided 2022-12-01 criteria provided, single submitter clinical testing MYH2: PVS1
GeneDx RCV003433116 SCV005333201 likely pathogenic not provided 2024-03-28 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33250842)

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