Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC related information was provided by the message!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000257.4(MYH7):c.341T>C (p.Ile114Thr)

CA013685

181300 (ClinVar)

Gene: MYH7
Condition: hypertrophic cardiomyopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 2a1f9856-ae11-4238-a6f1-2892ad8db5f8
Approved on: 2021-03-31
Published on: 2021-12-09

HGVS expressions

NM_000257.4:c.341T>C
NM_000257.4(MYH7):c.341T>C (p.Ile114Thr)
NC_000014.9:g.23433088A>G
CM000676.2:g.23433088A>G
NC_000014.8:g.23902297A>G
CM000676.1:g.23902297A>G
NC_000014.7:g.22972137A>G
NG_007884.1:g.7574T>C
ENST00000355349.4:c.341T>C
ENST00000355349.3:c.341T>C
NM_000257.3:c.341T>C
More

Uncertain Significance

Met criteria codes 3
PP3 PM2 PS4_Supporting
Not Met criteria codes 12
PP1 PM5 PM6 PM1 PS3 PS1 PS2 BA1 BP4 BS1 BS4 BS3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cardiomyopathy VCEP
The NM_000257.4(MYH7):c.341T>C (p.Ile114Thr) variant has been identified in 4 individuals with HCM (PS4_Supporting; Restrepo-Cordoba 2017 PMID:28138913; GeneDx pers. comm.; Invitae pers. comm.). This variant has also been identified in 1 individual with DCM who also carried a truncating variant in TTN and an individual with heart disease and sensory disfunction (Ambry pers. comm.; LMM pers. comm.). This variant was identified in 0.0009% (1/113612) of European chromosomes by gnomAD v2.1.1 (PM2; https://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may impact the protein (PP3). 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 (Kelly 2018 PMID:29300372): PS4_Supporting, PM2, PP3.
Met criteria codes
PP3
REVEL meta-predictor score is 0.896, above 0.75 threshold. Multiple predictors predict the variant is deleterious.
PM2
Subpopulation with highest frequency in gnomAD: 1/113612 for European (non-Finnish)
PS4_Supporting
4 HCM probands - 1 each from PMID: 28138913 and Invitae, and 2 from GeneDx 1 proband with DCM with TTN tv and 1 complex phenotype from Ambry No additional literature hits in ClinVar or Google Scholar.
Not Met criteria codes
PP1
No segregation data in literature or from internal data log
PM5
NM_000257.4(MYH7):c.341T>A (p.Ile114Asn) also in ClinVar, but listed as 1* VUS
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Not in the mutational hotspot of p.181-937
PS3
No functional evidence in the literature
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No segregation data in literature or from internal data log
BS3
No functional evidence in the literature
Curation History
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