S401A Summary

SCN5A S401A was found in 1 paper (see below) with a total of 0 carriers: 0 had BrS1, 0 had LQT3, and 0 had other disease. S401A is not present in gnomAD. S401A has been functionally characterized in 0 papers. Other variants at the same resdue are S401A .S401C .S401D .S401E .S401F .S401G .S401K .S401L .S401N .S401P .S401R .S401T .S401W .S401Y . 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 Mild_Hotspot region for Long QT syndrome.

S401A Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1720535420070000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

S401A 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
17205354 2007 HEK 95 -9 -2 NA

S401A 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 0.997 0.08497 1.43 0 0.927

S401A has 77 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
253 13.2
254 13.4
256 12.6
257 10.4
258 13.9
259 14.7
260 10.5
261 10.5
262 14.8
263 14.1 V263I
264 11.1
265 14.6
362 14
363 14.7
364 12.9
365 9.9
366 9.3
367 11.5 R367C R367H
368 7.6
369 4.2 M369K
370 6.7 T370M
371 6 Q371E
372 11.4
373 13.9
374 10.5
377 14.5
378 14.9
392 12.6
393 11.4
394 11
395 10.5
396 7
397 5 I397V
398 7.8
399 7.9
400 3.8 G400E G400R G400R
402 4.5 F402L F402L F402L
403 6.8
404 5.7
405 5.5
406 7.4 N406K N406K N406S
407 9.8
408 10.2
409 11.9 L409V
410 13.7
897 13.1
899 13.8
923 13.1
924 14.2 V924I
927 12.7 N927S
928 11.1
932 13.2
1650 12.6
1653 14.6
1654 14.3
1657 12.2
1658 14.7
1660 14.2 I1660V
1661 14.1 G1661R G1661R
1664 14
1705 13.6
1706 14.7
1708 12.5
1709 9.8 T1709M
1710 13 S1710L
1711 13.9
1759 14.7
1760 13.5
1763 14.4 V1763M
1764 10.5
1765 12.7
1767 9.4 Y1767C
1768 10.5 I1768V
1769 14.3
1770 14.2
1771 11.2
1772 13.9