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_000257.4(MYH7):c.1322C>T (p.Thr441Met)

CA010543

14122 (ClinVar)

Gene: MYH7
Condition: cardiomyopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 001b25ad-349a-401e-8256-78899c1526f5

HGVS expressions

NM_000257.4:c.1322C>T
NM_000257.4(MYH7):c.1322C>T (p.Thr441Met)
ENST00000355349.4:c.1322C>T
ENST00000355349.3:c.1322C>T
NM_000257.3:c.1322C>T
NC_000014.9:g.23429040G>A
CM000676.2:g.23429040G>A
NC_000014.8:g.23898249G>A
CM000676.1:g.23898249G>A
NC_000014.7:g.22968089G>A
NG_007884.1:g.11622C>T

Benign

Met criteria codes 2
PM1 BA1
Not Met criteria codes 24
PP4 PP2 PP1 PP3 PM6 PM4 PM5 PM2 PM3 PVS1 BS2 BS4 BS3 BS1 BP3 BP1 BP5 BP2 BP7 BP4 PS2 PS4 PS1 PS3

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cardiomyopathy VCEP
The c.1322C>T (p.Thr441Met) in MYH7 has been identified in 0.2% (FAF 95% CI; 47/18394) of East Asian chromosomes in gnomAD (BA1; https://gnomad.broadinstitute.org). While this variant lies in the head region of the protein (aa 181-937), where missense variants are statistically more likely to be disease-associated (PM1; Walsh 2017 PMID:27532257), this is not considered to be in conflict with BA1 since benign variation within this region was considered during that analysis. In summary, this variant meets criteria to be is classified as benign for cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): BA1, PM1.
Met criteria codes
PM1
Variant is located in head domain
BA1
Variant seen in 0.2% (FAF 95% CI; 51/19952) of East Asian chromosomes in gnomAD.
Not Met criteria codes
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
In silico analysis programs (SIFT, PolyPhen-2, Mutation Taster) give conflicting results with regards to a possible impact on the protein function.
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No other variants at this codon in ClinVar or HGMD.
PM2
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
PVS1
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
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
Expression studies showed that mutated and wild-type alleles were equally expressed at the mRNA level (PMID 17548557)
Not met. PubMed:17548557
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
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
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
BP7
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
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Variant reported in probands with HCM: unknown number from PMID 21426742, 21822976 (articles not available in English), and in 2 individuals with HCM (one of them carried also a pathogenic variant in MYBPC3), and 1 individual with borderline left ventricular hypertrophy (that also carried another variant in MYH7) from internal laboratories data from the ClinGen CMP working group. PS4 not met due to high allele frequency (BA1) Internal laboratory data reported one HCM case where the individual also carried a pathogenic variant in MYBPC3)
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
Not met. PubMed:17548557
Approved on: 2021-06-16
Published on: 2021-06-16
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.