MYH7 : c.4377G>T

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.4377G>Tp.K1459N (Lys > Asn)substitutionmissense chr14:23886504 (reverse strand)0.00030546

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.00030546 (ExAC mean allelic frequency), it is unlikely to be pathogenic.

HCM

OMGL: Detected in 5 / 3200 HCM patients - classified as Class 3-Unknown pathogenicity.

LMM:   Detected in 4 / 2912 HCM patients - classified as VUS favour pathogenic.

DCM

OMGL: Detected in 1 / 559 DCM patients - classified as Class 3-Unknown pathogenicity.

LMM:   Detected in 0 / 756 DCM patients.

For more information on the clinical significance of this variant, please see the ClinVar entry.

Detection in Population Databases



Database European African East Asian South Asian American Finnish Other Total
ExAC0.00051077
34 / 66566
0.00000000
0 / 10346
0.00000000
0 / 8642
0.00000000
0 / 16500
0.00025956
3 / 11558
0.00000000
0 / 6612
0.00000000
0 / 904
0.00030546
37 / 121128
ESP 0.00012
1 / 8600
0.00000
0 / 4406
0.00008
1 / 13006
1KG
0.00000
0 / 1006
0.00000
0 / 1322
0.00000
0 / 1008
0.00000
0 / 978
0.00000
0 / 694
0.00000
0 / 198
0.00000
0 / 5008

The Exome Aggregation Consortium (ExAC) is a database of 60,706 unrelated individuals sequenced as part of various disease-specific and population genetic studies. There is partial overlap between ExAC and 1000 Genomes (1KG) (1,851 of the 2,504 samples in 1KG) and the Exome Sequencing Project (ESP) (3,936 of the 6,500 samples in ESP).


Other Variant & Gene Details

Canonical Sequences
Transcript ENST00000355349 LRG_384t1NM_000257.2
Protein ENSP00000347507 LRG_384p1P12883

Missense Variant Predictions
SIFT Grantham Polyphen-DIV Polyphen-VAR Summary
62.5% of algorithms have predicted that this variant will adversely affect protein function
damaging moderately conservative probably damaging probably damaging
LRT MutationTaster MutationAssessor FATHMM
disease-causing high impact tolerated


References

1. Roddy Walsh, Kate L. Thomson, James S. Ware, Birgit H. Funke, Jessica Woodley, Karen J. McGuire, Francesco Mazzarotto, Edward Blair, Anneke Seller, Jenny C. Taylor, Eric V. Minikel, Exome Aggregation Consortium, Daniel G. MacArthur, Martin Farrall, Stuart A. Cook and Hugh Watkins. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 2016 doi:10.1038/gim.2016.90.

2. Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014 Aug;16(8):601-8.

3. Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet Med. 2015 Nov;17(11):880-8.