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  • See Evidence submitted by expert panel for details.

Variant: NM_000257.3(MYH7):c.1477_1478delAT (p.Met493Valfs)

CA010796

177817 (ClinVar)

Gene: MYH7
Condition: cardiomyopathy
Inheritance Mode: Autosomal dominant inheritance
UUID: 8d697e74-5cec-4ffa-a116-f83b4f8fb2b8
Approved on: 2021-11-30
Published on: 2021-12-09

HGVS expressions

NM_000257.3:c.1477_1478delAT
NM_000257.3(MYH7):c.1477_1478delAT (p.Met493Valfs)
NC_000014.9:g.23428600_23428601del
CM000676.2:g.23428600_23428601del
NC_000014.8:g.23897809_23897810del
CM000676.1:g.23897809_23897810del
NC_000014.7:g.22967649_22967650del
NG_007884.1:g.12061_12062del
ENST00000355349.4:c.1477_1478del
ENST00000355349.3:c.1477_1478del
NM_000257.3:c.1477_1478del
NM_000257.4:c.1477_1478del
NM_000257.4(MYH7):c.1477_1478del (p.Met493fs)
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Uncertain Significance

Met criteria codes 1
PM2
Not Met criteria codes 18
BA1 BS2 BS4 BS3 BS1 BP5 BP7 BP3 PS2 PS1 PS4 PVS1 PS3 PP1 PM6 PM1 PM4 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cardiomyopathy VCEP
The NM_000257.3(MYH7):c.1477_1478delAT (p.Met493Valfs) variant has been identified in 1 individual with features of both HCM and DCM (Zimmerman 2010 PMID:20474083; Walsh 2017 PMID: 27532257, LMM pers. comm.) however, this is insufficient to apply the PS4 criterion. This variant was absent from large population studies (PM2; http:// gnomad.broadinstitute.org, v.2.1.1). This variant is predicted to cause a frameshift leading to a truncated or absent protein. The contribution of loss of function (LOF) variants in MYH7 to autosomal dominant inherited cardiomyopathy is incompletely understood therefore PVS1 was not applied. In summary, due to insufficient evidence, this variant meets criteria to be classified as uncertain significance for cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): PM2.
Met criteria codes
PM2
Variant is absent from gnomAD v.2.1.1 with good coverage
Not Met criteria codes
BA1
Variant is absent from gnomAD v.2.1.1 with good coverage
BS2
n/a
BS4
n/a
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
Variant is absent from gnomAD v.2.1.1 with good coverage
BP5
n/a
BP7
variant is LOF
BP3
variant is LOF
PS2
n/a
PS1
variant is LOF
PS4
Variant identified in 1 case with cardiomyopathy (HCM and DCM; LMM ClinVar SCV000204119.3) HGMD: Zimmerman (2010) Genet Med 12: 268 PubMed: 20474083 Walsh (2017) Genet Med 19: 192 PubMed: 27532257 Kelly (2018) Genet Med 20: 351 PubMed: 29300372 Literature search complete: ClinVar, HGMD, Google LMM is only internal data
PVS1
will not include PVS1 until published info
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
n/a
PM6
n/a
PM1
n/a for this variant
PM4
variant is LOF
PM5
variant is LOF
Curation History
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