TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34200	102823;102824;102825	chr2:178534017;178534016;178534015	chr2:179398744;179398743;179398742
N2AB	32559	97900;97901;97902	chr2:178534017;178534016;178534015	chr2:179398744;179398743;179398742
N2A	31632	95119;95120;95121	chr2:178534017;178534016;178534015	chr2:179398744;179398743;179398742
N2B	25135	75628;75629;75630	chr2:178534017;178534016;178534015	chr2:179398744;179398743;179398742
Novex-1	25260	76003;76004;76005	chr2:178534017;178534016;178534015	chr2:179398744;179398743;179398742
Novex-2	25327	76204;76205;76206	chr2:178534017;178534016;178534015	chr2:179398744;179398743;179398742
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-160
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.1991
• 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
T/I	None	None	None	N	0.253	0.193	0.279776271856	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.21507E-04	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
T/A	0.1516	likely_benign	0.1527	benign	-0.773	Destabilizing	None	N	0.114	neutral	N	0.521167682	None	None	N
T/C	0.549	ambiguous	0.5922	pathogenic	-0.4	Destabilizing	0.676	D	0.434	neutral	None	None	None	None	N
T/D	0.4127	ambiguous	0.4065	ambiguous	-0.239	Destabilizing	0.038	N	0.414	neutral	None	None	None	None	N
T/E	0.3683	ambiguous	0.3485	ambiguous	-0.234	Destabilizing	None	N	0.129	neutral	None	None	None	None	N
T/F	0.5501	ambiguous	0.5623	ambiguous	-0.837	Destabilizing	0.038	N	0.452	neutral	None	None	None	None	N
T/G	0.269	likely_benign	0.2464	benign	-1.043	Destabilizing	0.016	N	0.405	neutral	None	None	None	None	N
T/H	0.338	likely_benign	0.3265	benign	-1.351	Destabilizing	0.001	N	0.31	neutral	None	None	None	None	N
T/I	0.5121	ambiguous	0.5493	ambiguous	-0.144	Destabilizing	None	N	0.253	neutral	N	0.491012382	None	None	N
T/K	0.2393	likely_benign	0.2233	benign	-0.753	Destabilizing	0.038	N	0.414	neutral	None	None	None	None	N
T/L	0.229	likely_benign	0.2353	benign	-0.144	Destabilizing	0.016	N	0.429	neutral	None	None	None	None	N
T/M	0.1939	likely_benign	0.2079	benign	0.196	Stabilizing	0.214	N	0.452	neutral	None	None	None	None	N
T/N	0.1449	likely_benign	0.1478	benign	-0.701	Destabilizing	0.029	N	0.303	neutral	N	0.512817558	None	None	N
T/P	0.5854	likely_pathogenic	0.5936	pathogenic	-0.321	Destabilizing	0.055	N	0.428	neutral	N	0.509205542	None	None	N
T/Q	0.2477	likely_benign	0.2258	benign	-0.839	Destabilizing	0.072	N	0.435	neutral	None	None	None	None	N
T/R	0.2115	likely_benign	0.1979	benign	-0.548	Destabilizing	0.072	N	0.438	neutral	None	None	None	None	N
T/S	0.1147	likely_benign	0.1101	benign	-0.972	Destabilizing	None	N	0.128	neutral	N	0.489479338	None	None	N
T/V	0.348	ambiguous	0.3601	ambiguous	-0.321	Destabilizing	0.016	N	0.309	neutral	None	None	None	None	N
T/W	0.8261	likely_pathogenic	0.8309	pathogenic	-0.797	Destabilizing	0.864	D	0.443	neutral	None	None	None	None	N
T/Y	0.5405	ambiguous	0.571	pathogenic	-0.561	Destabilizing	0.001	N	0.295	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.