Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

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Variant: NM_000257.4(MYH7):c.3020T>C (p.Leu1007Pro)

CA013309

181210 (ClinVar)

Gene: MYH7

Condition: dilated cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 7dacaca6-2df9-48d5-949d-8aadf64d5b9f

HGVS expressions

NM_000257.4:c.3020T>C

NM_000257.4(MYH7):c.3020T>C (p.Leu1007Pro)

NC_000014.9:g.23423626A>G

CM000676.2:g.23423626A>G

NC_000014.8:g.23892835A>G

CM000676.1:g.23892835A>G

NC_000014.7:g.22962675A>G

NG_007884.1:g.17036T>C

ENST00000355349.4:c.3020T>C

ENST00000355349.3:c.3020T>C

NM_000257.3:c.3020T>C

Uncertain Significance

PP3 PM2

PVS1 BA1 BS4 BS3 BS1 BP5 BP2 BP7 BP4 PS3 PS2 PS4 PS1 PP1 PM6 PM1 PM4 PM5

Evidence Links 0

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The NM_000257.4(MYH7):c.3020T>C (p.Leu1007Pro) variant has been identified in 1 individual with DCM and 1 individual with a complex cardiac presentation that included DCM (Ambry pers. comm., GeneDx pers. comm.) and segregated with non-compaction cardiomyopathy in 1 affected child (Ambry pers. comm); however, these data are currently insufficient to apply PS4 or establish co-segregation with disease and apply PP1. This variant was absent from large population studies (PM2; http://gnomad.broadinstitute.org, v2.1.1). 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 dilated cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): PM2, PP3.

PP3

BayesDel deleterious, revel>0.75

PM2

Variant absent in gnomAD with coverage

PVS1

Missense variant

BA1

Variant absent in gnomAD with coverage

BS4

no failure to segregate observed

BS3

No such studies

BS1

Variant absent in gnomAD with coverage

BP5

no alternate molecular basis for disease in either proband

BP2

not observed with other pathogenic variant

BP7

Missense variant

BP4

BayesDel deleterious

PS3

No such studies

PS2

no reported de novo

PS4

2 DCM probands from data curation log. one with a complex cardiac presentation that included DCM (Ambry pers. comm., GeneDx pers. comm.) ; however, these data are currently insufficient to apply PS4

PS1

No such pathogenic variant reported

PP1

1 possible meiosis, but relative young and phenotype not DCM

PM6

no reported de novo

PM1

Tail domain

PM4

Missense variant

PM5

No such pathogenic variant reported

Approved on: 2021-12-09

Published on: 2021-12-09

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