TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16413	49462;49463;49464	chr2:178614160;178614159;178614158	chr2:179478887;179478886;179478885
N2AB	14772	44539;44540;44541	chr2:178614160;178614159;178614158	chr2:179478887;179478886;179478885
N2A	13845	41758;41759;41760	chr2:178614160;178614159;178614158	chr2:179478887;179478886;179478885
N2B	7348	22267;22268;22269	chr2:178614160;178614159;178614158	chr2:179478887;179478886;179478885
Novex-1	7473	22642;22643;22644	chr2:178614160;178614159;178614158	chr2:179478887;179478886;179478885
Novex-2	7540	22843;22844;22845	chr2:178614160;178614159;178614158	chr2:179478887;179478886;179478885
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: Fn3-6
• Domain position: 63
• Structural Position: 94
• Q(SASA): 0.3328
• 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	0.454	D	0.461	0.302	0.286848849266	gnomAD-4.0.0	1.59389E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88437E-05	0	0	0	0
T/N	None	None	0.966	D	0.458	0.292	0.297718772494	gnomAD-4.0.0	1.59389E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41546E-04	0	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
T/A	0.0893	likely_benign	0.0831	benign	-0.571	Destabilizing	0.005	N	0.101	neutral	N	0.475639142	None	None	N
T/C	0.3376	likely_benign	0.3376	benign	-0.38	Destabilizing	0.974	D	0.502	neutral	None	None	None	None	N
T/D	0.4604	ambiguous	0.4523	ambiguous	0.381	Stabilizing	0.974	D	0.513	neutral	None	None	None	None	N
T/E	0.3795	ambiguous	0.3748	ambiguous	0.342	Stabilizing	0.842	D	0.484	neutral	None	None	None	None	N
T/F	0.2944	likely_benign	0.2916	benign	-0.843	Destabilizing	0.949	D	0.577	neutral	None	None	None	None	N
T/G	0.176	likely_benign	0.1623	benign	-0.763	Destabilizing	0.728	D	0.513	neutral	None	None	None	None	N
T/H	0.3024	likely_benign	0.3049	benign	-0.989	Destabilizing	0.998	D	0.552	neutral	None	None	None	None	N
T/I	0.2141	likely_benign	0.2162	benign	-0.174	Destabilizing	0.454	N	0.461	neutral	D	0.549988013	None	None	N
T/K	0.262	likely_benign	0.2638	benign	-0.431	Destabilizing	0.842	D	0.481	neutral	None	None	None	None	N
T/L	0.1037	likely_benign	0.1013	benign	-0.174	Destabilizing	0.007	N	0.203	neutral	None	None	None	None	N
T/M	0.1039	likely_benign	0.0996	benign	-0.016	Destabilizing	0.949	D	0.521	neutral	None	None	None	None	N
T/N	0.1199	likely_benign	0.1155	benign	-0.272	Destabilizing	0.966	D	0.458	neutral	D	0.522914919	None	None	N
T/P	0.1214	likely_benign	0.1204	benign	-0.276	Destabilizing	0.966	D	0.528	neutral	N	0.486369778	None	None	N
T/Q	0.2377	likely_benign	0.2353	benign	-0.451	Destabilizing	0.974	D	0.525	neutral	None	None	None	None	N
T/R	0.2471	likely_benign	0.2472	benign	-0.196	Destabilizing	0.974	D	0.525	neutral	None	None	None	None	N
T/S	0.0964	likely_benign	0.0951	benign	-0.586	Destabilizing	0.454	N	0.451	neutral	N	0.473464937	None	None	N
T/V	0.1341	likely_benign	0.1371	benign	-0.276	Destabilizing	0.029	N	0.105	neutral	None	None	None	None	N
T/W	0.6454	likely_pathogenic	0.6461	pathogenic	-0.784	Destabilizing	0.998	D	0.585	neutral	None	None	None	None	N
T/Y	0.355	ambiguous	0.3377	benign	-0.532	Destabilizing	0.991	D	0.571	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.