R367L Summary

SCN5A R367L was found in 2 papers (see below) with a total of 1 carrier: 1 had BrS1, 0 had LQT3, and 0 had other disease. R367L is not present in gnomAD. R367L has been functionally characterized in 1 paper. Other variants at the same resdue are R367C .R367G .R367H .R367L .R367P .R367S . Given the functional data available, we estimate this variant has "LOF" in vitro character. (LOF and GOF denote loss-of-function and gain-of-function, respectively). This residue is located in a Hotspot region for BrS1 and in a Mild_Hotspot region for Long QT syndrome.

R367L Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2012928320100100
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

R367L 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
32533946 2020 HEK NA NA

R367L 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 -6.87 probablydamaging 0.999 0.1234 -0.11 -8 0.951

R367L has 74 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
261 11.9
264 13.5
265 12.5
268 13.3
272 14
276 13.2 L276Q
347 13.9
348 12.6
349 11.4 D349N
350 12.5
351 13 G351S G351V
352 12
353 8.7 T353I
354 11
355 10.5 F355I
358 14.7
359 12.8
360 11.3
361 9.9
362 10.2
363 6.5
364 4.7
365 7.3
366 6.7
368 5.5
369 9 M369K
370 6.7 T370M
371 8.2 Q371E
372 4.5
373 6.1
374 7.6
375 10.1
376 9.3 R376H
377 6.4
378 11.7
379 12.9
380 11.6
381 12.4
392 12.8
393 10.8
396 10.8
397 10.8 I397V
400 13.4 G400E G400R G400R
401 11.5
402 14.9 F402L F402L F402L
404 15
405 14.3
893 12.9 R893C R893H
894 12.4
896 14.8
897 10.1
898 10.1
899 6.4
900 5.8
901 10.5 E901K
902 11.9
903 9.4
904 9
905 14.2
907 13.2
915 14.9
916 12
919 12.7
920 11.3
922 14.9
923 11.3
927 14.5 N927S
928 14.9
1419 13.7
1706 13.3
1709 12.7 T1709M
1710 13.9 S1710L
1711 12.1
1712 14.3 G1712S