V411M Summary

SCN5A V411M was found in 21 papers (see below) with a total of 18 carriers: 0 had BrS1, 17 had LQT3, and 1 had other disease. V411M is not present in gnomAD. V411M has been functionally characterized in 1 paper. Other variants at the same resdue are V411A .V411E .V411G .V411L .V411L .V411M . Given the functional data available, we estimate this variant has "Normal" in vitro character. (LOF and GOF denote loss-of-function and gain-of-function, respectively). This residue is located in a Mild_Hotspot region for BrS1 and in a Hotspot region for Long QT syndrome.

V411M Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2119306220110010
1096195520000010
1584047620050010
1671270220060010
2054104120100010
2236081720120010
2288591820120010
2309806720120040
2363143020130010
2460699520140010
2649671520160020
2649816020160001SD
2666966120161050
2694092520160010
2748556020160010
2901792720170000
2272156920120010
2688883820150000
2756675520160070
1971608520090030
30059973201800100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

V411M Reported Functional Data

Peak current and late current are relative % to wildtype. V0.5 act/inact are the voltages at which half of the maximal current is reached during an activation and inactivation protocol, each is in units of mV and relative to wildtype.

PMID Year Cell type Peak current V0.5 act V0.5 inact Rec from inact Late current
21193062 2011 HEK 100 -8.1 -7.9 175.8

V411M 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
Damaging 0 -2.94 probablydamaging 1 0.1002 -1.73 -1 0.947

V411M has 70 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
239 14.4 I239V I239V
241 12.8
242 10.1
243 11.2
244 12.2
245 9.2 Q245K
246 6.1
247 8.9 V247L V247L
248 10.9
249 6
250 6.1
251 10.2
252 10.5
253 8.2
254 10.8
255 14.1
256 12.9
257 13.1
403 14
404 10.9
405 10.5
406 9.7 N406K N406K N406S
407 6.5
408 5.7
409 6.5 L409V
410 4
412 4.4
413 5.9 A413T
414 4.8
415 6.4
416 10.6 Y416C
417 11.2
418 10.2
419 13.1
420 14.5
924 12.7 V924I
925 14.1
926 14.4
927 13.6 N927S
928 10.2
929 9.3
930 12.6
931 13.8
932 9.2
933 10.2
935 12
936 10.7
937 14.8
939 13.4
1470 14.7
1642 10.9
1643 11.7
1645 12.4 T1645M
1646 9.3
1647 13.3
1649 12.6
1650 12.7
1768 13 I1768V
1769 13.9
1771 11.1
1772 9.2
1773 12.9
1774 13.2
1775 7
1776 9.9
1777 13.4 V1777M
1778 12.1
1779 9.6 T1779M
1780 12.8
1782 14