Submissions for variant NM_000257.4(MYH7):c.4354-7C>T

dbSNP: rs370093487

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Cardiomyopathy Variant Curation Expert Panel	RCV000629073	SCV000564452	uncertain significance	Hypertrophic cardiomyopathy	2021-06-23	reviewed by expert panel	curation	The NM_000257.4(MYH7):c.4354-7C>T variant has been reported in 3 individuals with HCM (Invitae pers. comm; LMM pers. comm.). This variant has also been identified in 0.004% (FAF 95% CI; 4/34362) of Latino/Admixed American chromosomes by gnomAD v2.1.1 (https://gnomad.broadinstitute.org). Since the MYH7 specifications state that PS4 is only applicable if the variant is absent or rare in large population studies, the PS4 criterion was not applied (Kelly 2018 PMID:29300372). This variant is located in the 3' splice region and computational tools do not predict an impact on splicing, though this information is not predictive enough to rule out pathogenicity (BP4). In summary, due to insufficient evidence, this variant is classified as uncertain significance for hypertrophic cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): BP4.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035905	SCV000059556	uncertain significance	not specified	2011-07-25	criteria provided, single submitter	clinical testing	The 4354-7C>T variant has not been reported in the literature. This variant has been identified by our laboratory in two individuals with a clinical diagnosis a nd family history of HCM. Of note, this variant did not segregate with the famil y history of HCM in one of these family. The 4354-7C>T variant is located in the 3' splice acceptor region but does not affect the highly conserved -1 and -2 po sitions. However, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions can sometimes affect splicing. T herefore, the clinical significance of this variant cannot be determined at this time.
GeneDx	RCV000035905	SCV000170535	benign	not specified	2013-11-08	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000629073	SCV000749986	likely benign	Hypertrophic cardiomyopathy	2023-10-11	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001188648	SCV001355737	likely benign	Cardiomyopathy	2018-11-23	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001188648	SCV004817121	likely benign	Cardiomyopathy	2024-02-05	criteria provided, single submitter	clinical testing