E346D Summary

SCN5A E346D was found in 2 papers (see below) with a total of 1 carrier: 1 had BrS1, 0 had LQT3, and 0 had other disease. E346D is not present in gnomAD. E346D has been functionally characterized in 1 paper. Other variants at the same resdue are E346A .E346D .E346D .E346G .E346K .E346Q .E346V . 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 Hotspot region for BrS1 and in a Non_Hotspot region for Long QT syndrome.

E346D Reported Clinical Data

PMID Year Unaffected BrS LQT3 Other Other disease
1664339920060100
3253394620200000
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts.

E346D 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 113.2 -7.6 -4.1 1.692307692 NA

E346D 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
Tolerated 0.213 -1.28 benign 0 3.758 0.17 2 0.299

E346D has 42 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
273 14.7
274 11.1
275 13.7
276 10.8 L276Q
277 6.8
278 12.1
279 8.6
280 13.8
281 13.5 V281M
317 10.7
318 14.6
319 12.9 G319S
320 9.7 T320N
321 8.4
322 9
323 10.3
324 13.5
325 12.4
342 12.7
343 10.6
344 7
345 3.9
347 4.7
348 7.5
349 9.9 D349N
350 9.7
351 5.8 G351S G351V
352 9
353 9.8 T353I
354 9.9
355 14.4 F355I
356 11 D356N
357 13.7
360 12.2
380 13.7
871 14.6
872 13.7 D872N
904 13.1
908 12.9
912 14.7 Q912R
1550 11.9
1551 14.2 D1551N