LAMP2 in Hypertrophic Cardiomyopathy (HCM)

The role of rare variants in LAMP2 as causative mutations in Hypertrophic Cardiomyopathy is described below. By comparing the frequency of LAMP2 variants in large HCM clinical cohorts to the background population rate in the ExAC database, the proportion of HCM patients with pathogenic mutations in LAMP2 can be estimated, as well as the likelihood that a rare (population allele frequency <0.0001) LAMP2 variant identified in a HCM patient is disease-causing. Summary data for different variant classes (all protein-altering variants, loss of function truncating variants and non-truncating variants) is highlighted - see the table below for full details of this analysis.

Excess of LAMP2 variants in HCM: 0.44% (p<0.0001)

Based on an analysis of all rare protein-altering variants (MAF<0.0001 in ExAC) in LAMP2 found in 3290 HCM samples sequenced by OMGL and LMM and in reference samples of the ExAC population database.

Metrics by Variant Class:
All VarsTruncatingNon-Truncating
Excess in HCM 0.44%
Etiological fraction 0.69
0.48 - 0.81
0.97 - 1.00
0.00 - 0.60
Odds Ratio 3.23
1.93 - 5.18

0.52 - 2.50

The Etiological Fraction (EF) is the proportion of affected carriers where the variant caused HCM. The Odds Ratio (OR) describes the odds of having a rare variant in the patient cohort to the odds in the ExAC cohort. Fisher's exact test p-values are displayed for case excess, 95% confidence intervals for EFs and ORs.

in HCM
in ExAC
Case Excess
in HCM
(OMGL1 + LMM2)
3290All21 0.006380.001980.00440
Truncating13 0.003950.000000.00395
Non-Truncating8 0.002430.001980.00045
OMGL1839All11 0.013110.001980.01113
Truncating9 0.010730.000000.01073
Non-Truncating2 0.002380.001980.00040
LMM22451All10 0.004080.001980.00210
Truncating4 0.001630.000000.00163
Non-Truncating6 0.002450.001980.00047


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