Variant: NM_000257.4(MYH7):c.1888+1G>A

CA011391

180441 (ClinVar)

Gene: MYH7

Condition: cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

UUID: eae5fc5c-c5da-4ed7-b60c-08fefb81f891

Approved on: 2021-09-22

Published on: 2021-10-01

HGVS expressions

NM_000257.4:c.1888+1G>A
NM_000257.4(MYH7):c.1888+1G>A
ENST00000355349.4:c.1888+1G>A
ENST00000355349.3:c.1888+1G>A
NM_000257.3:c.1888+1G>A
NC_000014.9:g.23427584C>T
CM000676.2:g.23427584C>T
NC_000014.8:g.23896793C>T
CM000676.1:g.23896793C>T
NC_000014.7:g.22966633C>T
NG_007884.1:g.13078G>A

Uncertain Significance

• Met criteria codes: PM2

• Not Met criteria codes: PM6 PM1 PM5 PM3 BS2 PVS1 BS4 BS3 BS1 BP5 BP2 BP4 BP1 PS2 PS4 PS1 PS3 BA1 PP4 PP2 PP1 PP3

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Evidence submitted by expert panel

Cardiomyopathy VCEP

The NM_000257.4(MYH7):c.1888+1G>A variant has been identified in at least 1 individual with LVNC and a reduced ejection fraction (GeneDx pers. comm.); however, this is insufficient to apply the PS4 criterion. This variant was identified in 0.003% (1/30600) of South Asian chromosomes by gnomAD v2.1.1 (PM2; https://gnomad.broadinstitute.org). This splice variant is predicted to abolish the canonical splice site and impact splicing, which often leads to a truncated or absent protein; however, the contribution of LOF variants in MYH7 to autosomal dominant inherited cardiomyopathy is incompletely understood and therefore PVS1 was not applied. In summary, due to insufficient evidence, this variant is 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 has been identified in 0.003% (1/30600) of South Asian chromosomes

Not Met criteria codes

• PM6: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PVS1: LoF is not a recognised mechanism of disease for MYH7
• BS4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS3: 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
• BP5: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP2: 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
• BP1: 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
• PS4: No articles identified in ClinVar, HGMD, or via Google Scholar search. - mak GeneDx has seen this in 1 proband with LVNC and decreased EF.
• PS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PS3: 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
• PP4: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline