TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14923	44992;44993;44994	chr2:178624513;178624512;178624511	chr2:179489240;179489239;179489238
N2AB	13282	40069;40070;40071	chr2:178624513;178624512;178624511	chr2:179489240;179489239;179489238
N2A	12355	37288;37289;37290	chr2:178624513;178624512;178624511	chr2:179489240;179489239;179489238
N2B	5858	17797;17798;17799	chr2:178624513;178624512;178624511	chr2:179489240;179489239;179489238
Novex-1	5983	18172;18173;18174	chr2:178624513;178624512;178624511	chr2:179489240;179489239;179489238
Novex-2	6050	18373;18374;18375	chr2:178624513;178624512;178624511	chr2:179489240;179489239;179489238
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-100
• Domain position: 71
• Structural Position: 155
• Q(SASA): 0.158
• 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/S	rs760857643	-1.514	0.955	N	0.482	0.174	0.240491677333	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
T/S	rs760857643	-1.514	0.955	N	0.482	0.174	0.240491677333	gnomAD-4.0.0	1.36929E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79987E-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
T/A	0.2812	likely_benign	0.1691	benign	-1.368	Destabilizing	0.117	N	0.34	neutral	N	0.392843886	None	None	N
T/C	0.8037	likely_pathogenic	0.6959	pathogenic	-0.812	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
T/D	0.8403	likely_pathogenic	0.8163	pathogenic	-1.637	Destabilizing	0.998	D	0.748	deleterious	None	None	None	None	N
T/E	0.6655	likely_pathogenic	0.6837	pathogenic	-1.382	Destabilizing	0.995	D	0.711	prob.delet.	None	None	None	None	N
T/F	0.5955	likely_pathogenic	0.528	ambiguous	-1.0	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
T/G	0.7087	likely_pathogenic	0.5605	ambiguous	-1.794	Destabilizing	0.966	D	0.621	neutral	None	None	None	None	N
T/H	0.5725	likely_pathogenic	0.5457	ambiguous	-1.708	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
T/I	0.3657	ambiguous	0.3748	ambiguous	-0.221	Destabilizing	0.993	D	0.75	deleterious	N	0.405387493	None	None	N
T/K	0.623	likely_pathogenic	0.6369	pathogenic	-0.119	Destabilizing	0.995	D	0.706	prob.neutral	None	None	None	None	N
T/L	0.3676	ambiguous	0.299	benign	-0.221	Destabilizing	0.983	D	0.557	neutral	None	None	None	None	N
T/M	0.2397	likely_benign	0.186	benign	-0.361	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
T/N	0.4438	ambiguous	0.3947	ambiguous	-0.956	Destabilizing	0.997	D	0.672	neutral	N	0.481980813	None	None	N
T/P	0.9269	likely_pathogenic	0.9139	pathogenic	-0.576	Destabilizing	0.997	D	0.775	deleterious	D	0.553167403	None	None	N
T/Q	0.5326	ambiguous	0.5105	ambiguous	-0.654	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
T/R	0.4978	ambiguous	0.475	ambiguous	-0.476	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
T/S	0.2661	likely_benign	0.1927	benign	-1.229	Destabilizing	0.955	D	0.482	neutral	N	0.346376975	None	None	N
T/V	0.3185	likely_benign	0.283	benign	-0.576	Destabilizing	0.966	D	0.458	neutral	None	None	None	None	N
T/W	0.8839	likely_pathogenic	0.8689	pathogenic	-1.141	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
T/Y	0.647	likely_pathogenic	0.5976	pathogenic	-0.747	Destabilizing	0.999	D	0.815	deleterious	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.