TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14615	44068;44069;44070	chr2:178631205;178631204;178631203	chr2:179495932;179495931;179495930
N2AB	12974	39145;39146;39147	chr2:178631205;178631204;178631203	chr2:179495932;179495931;179495930
N2A	12047	36364;36365;36366	chr2:178631205;178631204;178631203	chr2:179495932;179495931;179495930
N2B	5550	16873;16874;16875	chr2:178631205;178631204;178631203	chr2:179495932;179495931;179495930
Novex-1	5675	17248;17249;17250	chr2:178631205;178631204;178631203	chr2:179495932;179495931;179495930
Novex-2	5742	17449;17450;17451	chr2:178631205;178631204;178631203	chr2:179495932;179495931;179495930
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-97
• Domain position: 30
• Structural Position: 45
• Q(SASA): 0.7767
• 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
P/L	rs1281092990	0.005	0.92	D	0.624	0.615	0.692581660658	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
P/L	rs1281092990	0.005	0.92	D	0.624	0.615	0.692581660658	gnomAD-4.0.0	2.05345E-06	None	None	None	None	N	None	2.989E-05	0	None	0	0	None	0	0	1.79925E-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
P/A	0.1032	likely_benign	0.0985	benign	-0.501	Destabilizing	0.826	D	0.428	neutral	D	0.660822796	None	None	N
P/C	0.7435	likely_pathogenic	0.7333	pathogenic	-0.499	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
P/D	0.4085	ambiguous	0.3661	ambiguous	-0.429	Destabilizing	0.02	N	0.22	neutral	None	None	None	None	N
P/E	0.2929	likely_benign	0.2509	benign	-0.527	Destabilizing	0.17	N	0.245	neutral	None	None	None	None	N
P/F	0.6484	likely_pathogenic	0.616	pathogenic	-0.688	Destabilizing	0.997	D	0.619	neutral	None	None	None	None	N
P/G	0.48	ambiguous	0.4525	ambiguous	-0.655	Destabilizing	0.969	D	0.51	neutral	None	None	None	None	N
P/H	0.2817	likely_benign	0.246	benign	-0.263	Destabilizing	0.991	D	0.585	neutral	None	None	None	None	N
P/I	0.4168	ambiguous	0.3989	ambiguous	-0.237	Destabilizing	0.997	D	0.623	neutral	None	None	None	None	N
P/K	0.3462	ambiguous	0.3141	benign	-0.479	Destabilizing	0.884	D	0.459	neutral	None	None	None	None	N
P/L	0.1648	likely_benign	0.1611	benign	-0.237	Destabilizing	0.92	D	0.624	neutral	D	0.622151802	None	None	N
P/M	0.4467	ambiguous	0.4388	ambiguous	-0.325	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	N
P/N	0.4129	ambiguous	0.3669	ambiguous	-0.183	Destabilizing	0.939	D	0.565	neutral	None	None	None	None	N
P/Q	0.2425	likely_benign	0.2079	benign	-0.406	Destabilizing	0.31	N	0.291	neutral	D	0.533742519	None	None	N
P/R	0.2534	likely_benign	0.23	benign	0.015	Stabilizing	0.976	D	0.599	neutral	D	0.589371977	None	None	N
P/S	0.1602	likely_benign	0.1449	benign	-0.513	Destabilizing	0.92	D	0.445	neutral	D	0.576789001	None	None	N
P/T	0.1227	likely_benign	0.1225	benign	-0.51	Destabilizing	0.959	D	0.506	neutral	D	0.582348422	None	None	N
P/V	0.304	likely_benign	0.2961	benign	-0.29	Destabilizing	0.969	D	0.578	neutral	None	None	None	None	N
P/W	0.8008	likely_pathogenic	0.775	pathogenic	-0.804	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
P/Y	0.6129	likely_pathogenic	0.5727	pathogenic	-0.496	Destabilizing	0.997	D	0.621	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.