M438L Summary

SCN5A M438L was found in 1 paper (see below) with a total of 1 carrier: 1 had BrS1, 0 had LQT3, and 0 had other disease. M438L is not present in gnomAD. M438L has been functionally characterized in 0 papers. Other variants at the same resdue are M438I .M438I .M438I .M438K .M438L .M438L .M438R .M438T .M438V . This residue is located in a Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

M438L Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2970910120180100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

M438L Predictions

PROVEAN scores less than -2 are considered deleterious. REVEL scores higher than 0.5 or 0.75 is considered likely pathogenic (higher sensitivity with the former cutoff, higher specificity with the latter cutoff). A PolyPhen-2 score of 0.85 or greater is considered likely pathogenic. PAM scores reflect the chemistry difference between WT and variant amino acid (more negative being greater difference between the two). BLAST-PSSM reflects the evolutionary conservation of residue substitutions, more negative numbers indicate fewer observations of the specific substitution than is expected.

SIFT Sift Score PROVEAN Score Polyphen2 Polyphen2 Score eaRate blastPssm pamScore REVEL
Tolerated 1 0.45 benign 0 1.51 1.5 1 0.31

M438L has 30 neighbors within 15 ångströms that have been found in individuals.

A residue within a folded protein on average has nearest neighbors that fall roughly into two shells: a "nearest" neighbor around 5-6 angstroms and a second shell around 11 angstroms.

ResidueNumber Distance(Å) Variants
423 14.7
424 14.2 I424M
425 13.7
426 13.2
427 12.6
428 12 E428K
429 11.4 E429K p.E429del
430 10.7
431 10.1
432 9.3
433 8.5 R433C
434 7.6
435 6.6
436 5.4
437 3.8
439 3.8
440 5.4
441 6.6
442 7.6
443 8.5
444 9.3
445 10.1 H445D
446 10.7 E446K
447 11.4 A447G
448 12
449 12.6 T449A
450 13.2
451 13.7
452 14.2
453 14.7 V453M