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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000257.3(MYH7):c.4377G>T (p.Lys1459Asn)

CA014901

43012 (ClinVar)

Gene: MYH7

Condition: cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: dfd5170f-2105-4cc6-870a-2f7511d716cd

Approved on: 2016-12-15

Published on: 2018-11-16

HGVS expressions

NM_000257.3:c.4377G>T

NM_000257.3(MYH7):c.4377G>T (p.Lys1459Asn)

NC_000014.9:g.23417295C>A

CM000676.2:g.23417295C>A

NC_000014.8:g.23886504C>A

CM000676.1:g.23886504C>A

NC_000014.7:g.22956344C>A

NG_007884.1:g.23367G>T

NR_126491.1:n.735C>A

NM_000257.4:c.4377G>T

ENST00000355349.3:c.4377G>T

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Conflicting Evidence"

BS1 PP3

Evidence Links 0

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The filtering allele frequency of the c.4377G>T (p.Lys1459Asn) variant in the MYH7 gene is 0.0375% (34/66566) of European chromosomes by the Exome Aggregation Consortium (http://exac.broadinstitute.org), which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BS1; PMID:29300372). Additionally, while computational prediction tools and conservation analysis suggest that this variant may impact the protein (PP3), this pathogenic evidence code (PP3) was not considered to be in conflict with a likely benign conclusion given the accuracy of computation prediction tools. In summary, this variant meets criteria to be classified as likely benign for cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): PP3; BS1

BS1

Filtering allele frequency of 0.0375% in Europeans in ExAC

PP3

Tools predict damaging

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