G351V Summary

SCN5A G351V was found in 2 papers (see below) with a total of 3 carriers: 3 had BrS1, 0 had LQT3, and 0 had other disease. G351V is not present in gnomAD. G351V has been functionally characterized in 1 paper. Other variants at the same resdue are G351A .G351C .G351D .G351R .G351S .G351V . 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.

G351V Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1205196320020300
2012928320100100
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

G351V 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
12051963 2002 HEK-tSA204 14.2 2.1 NA

G351V 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 -7.79 probablydamaging 1 0.5892 -2.16 -5 0.972

G351V has 56 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
272 14.8
273 14.6
274 11.8
275 14.1
276 9.9 L276Q
277 8.8
278 14.1
279 12.1
321 12.6
322 11
323 12.6
324 14.4
325 13.1
343 13.9
344 11.7
345 9.2
346 5.8 E346K
347 3.8
348 5.8
349 6.6 D349N
350 5.5
352 3.7
353 5.4 T353I
354 6.9
355 11.4 F355I
356 9.7 D356N
357 11.2
359 11.9
360 7.7
361 11.9
363 11.1
364 11.5
367 13 R367C R367H
376 12.4 R376H
377 12.3
380 11.8
381 14.7
871 13.3
872 13.3 D872N
900 11.7
901 13.1 E901K
902 14.7
903 11.9
904 7.5
905 11.7
906 13.6
907 10.1
908 9.5
909 13.6
910 14.9 S910L
911 12.7
912 10.5 Q912R
915 14.9
916 14.1
1549 15
1550 13.2