P336L Summary

SCN5A P336L was found in 6 papers (see below) with a total of 3 carriers: 1 had BrS1, 0 had LQT3, and 0 had other disease. P336L is not present in gnomAD. P336L has been functionally characterized in 2 papers. Other variants at the same resdue are P336A .P336L .P336Q .P336R .P336S .P336T . Given the functional data available, we estimate this variant has "Partial_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 Non_Hotspot region for Long QT syndrome.

P336L Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1707501620062100
2426915920131100
2617311120150100
2012928320100100
2012928320100100
3005997320180010
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

P336L 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
17075016 2006 HEK-tSA201 15.1 1.7 -1.5 NA NA
24269159 2013 HEK 20 0 NA

P336L 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 0.012 -9.68 probablydamaging 0.998 0.9259 -2.24 -7 0.916

P336L has 31 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
278 13.7
279 12.4
280 7
281 9.7 V281M
282 9.1 R282C R282H
283 11.2
284 12.8
285 14.6
323 11.6
324 10.7
325 11.9
326 7.5
327 9.8
328 12.1
329 14
332 12.2 A332T
333 9.6
334 6.9
335 3.7 C335R
337 5.9
338 6.2
339 4.4
340 9.9 R340Q R340W
341 10.1 C341Y
342 12.5
383 11.4
384 13.8
1684 14.2
1689 12.9
1690 11.9 D1690N
1691 13.7