G386R Summary

SCN5A G386R was found in 3 papers (see below) with a total of 2 carriers: 2 had BrS1, 0 had LQT3, and 0 had other disease. G386R is not present in gnomAD. G386R has been functionally characterized in 1 paper. Other variants at the same resdue are G386A .G386E .G386R .G386R .G386V .G386W . 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 Non_Hotspot region for Long QT syndrome.

G386R Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
2617311120150100
2012928320100100
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

G386R 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 1.2 NA

G386R 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 -7.85 probablydamaging 1 0.06826 -2.23 -9 0.981

G386R has 57 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
268 13.4
271 10.8
272 9.5
274 13.3
275 9.8
276 10.9 L276Q
278 11.3
324 14.4
325 10.7
326 10.9
327 8.9
328 9.4
329 6.3
330 7.5
331 7.6
332 5.5 A332T
333 8.4
334 10.7
335 14.2 C335R
341 13.5 C341Y
355 13.7 F355I
374 14.3
375 14.9
377 12.2
378 8.6
379 10.3
380 10.6
381 6.2
382 3.8
383 8.4
384 6.2
385 3.5 A385T
387 5.1
388 5
389 4.8
390 8
391 10
392 10.5
393 9.9
394 13.1
395 14.8
1620 13.1 T1620K T1620M
1689 12.9
1690 14.6 D1690N
1691 8.9
1692 10.3
1693 14.1
1696 14.4
1697 14.4
1698 11 A1698T
1699 10.9
1700 14.4
1701 13.2 M1701I M1701I M1701I
1702 9.3
1703 13.5
1705 12.9
1706 13.9