Submissions for variant NM_000257.4(MYH7):c.3854-5C>T

gnomAD frequency: 0.00002  dbSNP: rs752385694

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001177082	SCV001341215	likely benign	Cardiomyopathy	2019-04-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001375551	SCV001572420	uncertain significance	not specified	2021-04-09	criteria provided, single submitter	clinical testing	Variant summary: MYH7 c.3854-5C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.2e-05 in 251484 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3854-5C>T has been reported in the literature in one pediatric cardiomyopathy patient with diastolic dysfunction (Quan_2019). The report does not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae	RCV001483851	SCV001688258	likely benign	Hypertrophic cardiomyopathy	2024-01-21	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001177082	SCV004239463	uncertain significance	Cardiomyopathy	2022-07-06	criteria provided, single submitter	clinical testing