ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.5655+5G>C

dbSNP: rs1595070689
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations RCV000855671 SCV000998574 pathogenic Primary dilated cardiomyopathy; Congenital myopathy 2019-02-02 criteria provided, single submitter clinical testing The intronic c.5655+5G>C variant was not reported in any previous studies to our knowledge and is absent from large population studies (gnomAD/ExAC no frequency). The other intronic substitution at this position c.5655+5G>A was reported on the ClinVar (Variation ID:662627). This variant was observed in individual with congenital myopathy and drop head syndrome with de novo confirmation. Evaluation of c.5655+5G>C variant at our clinical center was done with experimental data (DOI:10.1016/j.gene.2019.02.011). The data demonstrated that an intronic variant c.5655+5G>C in the MYH7 gene leads to breaking the donor splice site, resulting in the skipping of exon 38 in the mRNA. Based on this evidences the c.5655+5G>C variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV002538879 SCV003484137 likely pathogenic Hypertrophic cardiomyopathy 2022-01-15 criteria provided, single submitter clinical testing This sequence change falls in intron 38 of the MYH7 gene. It does not directly change the encoded amino acid sequence of the MYH7 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with autosomal dominant MYH7-related conditions (PMID: 30794915). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 694311). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 38, but is expected to preserve the integrity of the reading-frame (PMID: 30794915). 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.

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