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]
Link to SEPIO compliant JSON-LD document
  • See Evidence submitted by expert panel for details.

Variant: NM_000257.3(MYH7):c.5704G>C (p.Glu1902Gln)

CA016398

43082 (ClinVar)

Gene: MYH7
Condition: cardiomyopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 4d5712d1-cc9f-4b7f-a73c-73dcffcd7849
Approved on: 2021-03-22
Published on: 2021-08-25

HGVS expressions

NM_000257.3:c.5704G>C
NM_000257.3(MYH7):c.5704G>C (p.Glu1902Gln)
ENST00000355349.4:c.5704G>C
ENST00000355349.3:c.5704G>C
NM_000257.4:c.5704G>C
NC_000014.9:g.23413845C>G
CM000676.2:g.23413845C>G
NC_000014.8:g.23883054C>G
CM000676.1:g.23883054C>G
NC_000014.7:g.22952894C>G
NG_007884.1:g.26817G>C

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"
Met criteria codes 1
BS1
Not Met criteria codes 14
PS3 PS2 PS1 PS4 PP1 PP3 PM6 PM1 PM5 PM2 BA1 BS4 BS3 BP4

Evidence Links 2

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cardiomyopathy VCEP
The c.5704G>C (p.Glu1902Gln) variant in MYH7 has been identified in 0.096% (FAF 95% CI; 27/19954) of East Asian chromosomes in gnomAD v2.1.1 (https://gnomad.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; Kelly 2018 PMID:29300372). Allowing a variant to reach a likely benign classification based on BS1 alone represents a revision of the original ACMG/AMP framework by ClinGen’s Sequence Variant Interpretation Working Group (Tavtigian 2018 PMID: 29300386). 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 (Kelly 2018 PMID:29300372): BS1
Met criteria codes
BS1
This variant was identified in 0.096% (FAF 95% CI; 27/19954) of East Asian chromosomes in gnomAD v2.1.1 (https://gnomad.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).
Not Met criteria codes
PS3
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
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
5 probands with HCM total (including ClinVar SCV000059629.5 and SHaRe data) - but PS4 not applied as PM2 criterion was not met INDIVIDUAL DATA: Invitae: No proband count provided since LB OMGL: 1 proband with HCM, likely same as Walsh 2017 (PMID: 27532257) Ingles: Seen in 1 family (assumed to be HCM) Ambry: Seen in 1 proband with HCM CHEO: 1 proband with HCM GeneDx: 1 proband who also had MYBPC3 nonsense variant
Variant identified in proband with HCM PubMed:27532257
Variant identified in proband with HCM PubMed:25086479
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
Computational tools are mixed
PM6
No de novo data
PM1
Outside of head domain
PM5
NM_000257.4(MYH7):c.5704G>A (p.Glu1902Lys): In ClinVar - VUS by GeneDx (2016) and LabCorp (2017); Also listed in HGMD as in Zimmerman (2010; PMID: 20474083) from the LMM. Did not investigate further.
PM2
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
BS4
No segregation data
BS3
No functional data
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.