Implicated in causing dilated cardiomyopathy, but seen in also seen in some unaffected controls with no family history of heart disease. The significance of this variant is unclear; if it is involved in the disease, the increased risk seems to be very low and may require other genetic or environmental factors.
EVS data reports this variant as having 0.4% allele frequency (0.8% of individuals are carriers). This is very discordant with the prevalence of DCM (0.04%).
Data from Knoll et al. and Geier et al. implies that, if this variant is involved in the disease, it is found in 1-2% of cases — and so .0008% of individuals are estimated to have DCM and be a carrier (.04% * 2%). To be consistent with the allele frequency data, this would mean only around 0.002% of carriers develop the disease.
Edited in this revision:
Seen in 10 out of 526 DCM cases with European ethnic origin, and not seen in 320 age-matched European controls. The authors report this as “P < 0.01 by exact Fisher test”, but we calculate it to be p = 0.016 using a two-tailed Fisher’s Exact test.
In functional studies, the authors report that “the W4R mutation in MLP results in the complete loss of T-cap binding”.
| Cases/controls | case+ | case– | control+ | control– | p-value | odds ratio |
|---|
Dilated Cardiomyopathy
| 10 |
516 |
0 |
320 |
0.0164 |
∞ |
Testing 652 DCM and 354 HCM patients, and 1066 chromosomes of control probands (= 533 individuals) this variant was seen in 3 DCM cases, 2 HCM, and 2 controls.
One of the three DCM families was found to have a different causative mutation (MYBPC3-Q1233X). The two controls were found to have a negative family history of heart failure. The authors conclude that “the W4R variant is not sufficient to cause cardiomyopathy”.
| Cases/controls | case+ | case– | control+ | control– | p-value | odds ratio |
|---|
Dilated Cardiomyopathy
| 3 |
649 |
2 |
531 |
1.0000 |
1.227 |