TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2272	7039;7040;7041	chr2:178774450;178774449;178774448	chr2:179639177;179639176;179639175
N2AB	2272	7039;7040;7041	chr2:178774450;178774449;178774448	chr2:179639177;179639176;179639175
N2A	2272	7039;7040;7041	chr2:178774450;178774449;178774448	chr2:179639177;179639176;179639175
N2B	2226	6901;6902;6903	chr2:178774450;178774449;178774448	chr2:179639177;179639176;179639175
Novex-1	2226	6901;6902;6903	chr2:178774450;178774449;178774448	chr2:179639177;179639176;179639175
Novex-2	2226	6901;6902;6903	chr2:178774450;178774449;178774448	chr2:179639177;179639176;179639175
Novex-3	2272	7039;7040;7041	chr2:178774450;178774449;178774448	chr2:179639177;179639176;179639175

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-12
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.6771
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
E/K	None	None	0.92	N	0.445	0.28	0.326616659874	gnomAD-4.0.0	1.59336E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85727E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
E/A	0.0971	likely_benign	0.105	benign	-0.931	Destabilizing	0.826	D	0.423	neutral	N	0.475980209	None	None	N
E/C	0.7355	likely_pathogenic	0.7585	pathogenic	-0.411	Destabilizing	0.999	D	0.406	neutral	None	None	None	None	N
E/D	0.1169	likely_benign	0.1196	benign	-0.743	Destabilizing	0.704	D	0.45	neutral	N	0.473744782	None	None	N
E/F	0.6218	likely_pathogenic	0.6468	pathogenic	-0.292	Destabilizing	0.964	D	0.43	neutral	None	None	None	None	N
E/G	0.0969	likely_benign	0.1037	benign	-1.269	Destabilizing	0.92	D	0.444	neutral	N	0.412816584	None	None	N
E/H	0.3905	ambiguous	0.3961	ambiguous	-0.403	Destabilizing	0.1	N	0.203	neutral	None	None	None	None	N
E/I	0.2645	likely_benign	0.2807	benign	-0.014	Destabilizing	0.991	D	0.441	neutral	None	None	None	None	N
E/K	0.1152	likely_benign	0.1156	benign	-0.3	Destabilizing	0.92	D	0.445	neutral	N	0.458897817	None	None	N
E/L	0.264	likely_benign	0.2851	benign	-0.014	Destabilizing	0.939	D	0.437	neutral	None	None	None	None	N
E/M	0.3255	likely_benign	0.3507	ambiguous	0.348	Stabilizing	0.999	D	0.395	neutral	None	None	None	None	N
E/N	0.1633	likely_benign	0.1715	benign	-0.836	Destabilizing	0.17	N	0.164	neutral	None	None	None	None	N
E/P	0.1993	likely_benign	0.2154	benign	-0.299	Destabilizing	0.046	N	0.189	neutral	None	None	None	None	N
E/Q	0.1169	likely_benign	0.1206	benign	-0.717	Destabilizing	0.959	D	0.427	neutral	N	0.487637419	None	None	N
E/R	0.2324	likely_benign	0.2306	benign	0.007	Stabilizing	0.969	D	0.41	neutral	None	None	None	None	N
E/S	0.1397	likely_benign	0.1479	benign	-1.119	Destabilizing	0.939	D	0.413	neutral	None	None	None	None	N
E/T	0.144	likely_benign	0.1581	benign	-0.83	Destabilizing	0.939	D	0.404	neutral	None	None	None	None	N
E/V	0.1447	likely_benign	0.1571	benign	-0.299	Destabilizing	0.92	D	0.444	neutral	N	0.493415866	None	None	N
E/W	0.8514	likely_pathogenic	0.8612	pathogenic	0.055	Stabilizing	0.999	D	0.396	neutral	None	None	None	None	N
E/Y	0.4883	ambiguous	0.5049	ambiguous	-0.007	Destabilizing	0.17	N	0.294	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.