TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21937	66034;66035;66036	chr2:178582994;178582993;178582992	chr2:179447721;179447720;179447719
N2AB	20296	61111;61112;61113	chr2:178582994;178582993;178582992	chr2:179447721;179447720;179447719
N2A	19369	58330;58331;58332	chr2:178582994;178582993;178582992	chr2:179447721;179447720;179447719
N2B	12872	38839;38840;38841	chr2:178582994;178582993;178582992	chr2:179447721;179447720;179447719
Novex-1	12997	39214;39215;39216	chr2:178582994;178582993;178582992	chr2:179447721;179447720;179447719
Novex-2	13064	39415;39416;39417	chr2:178582994;178582993;178582992	chr2:179447721;179447720;179447719
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-125
• Domain position: 72
• Structural Position: 157
• Q(SASA): 0.2281
• 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/A	rs969062428	None	0.76	N	0.625	0.214	0.324436698001	gnomAD-4.0.0	1.70846E-06	None	None	None	None	N	None	0	2.51813E-05	None	0	0	None	0	0	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	0.1171	likely_benign	0.108	benign	-1.007	Destabilizing	0.76	D	0.625	neutral	N	0.487378304	None	None	N
T/C	0.3719	ambiguous	0.3339	benign	-0.903	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
T/D	0.5741	likely_pathogenic	0.5502	ambiguous	-1.316	Destabilizing	0.998	D	0.812	deleterious	None	None	None	None	N
T/E	0.3405	ambiguous	0.3284	benign	-1.244	Destabilizing	0.993	D	0.796	deleterious	None	None	None	None	N
T/F	0.2203	likely_benign	0.2045	benign	-1.047	Destabilizing	0.993	D	0.844	deleterious	None	None	None	None	N
T/G	0.4501	ambiguous	0.4207	ambiguous	-1.308	Destabilizing	0.993	D	0.792	deleterious	None	None	None	None	N
T/H	0.2505	likely_benign	0.2259	benign	-1.625	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
T/I	0.105	likely_benign	0.1004	benign	-0.272	Destabilizing	0.322	N	0.499	neutral	N	0.469048138	None	None	N
T/K	0.2453	likely_benign	0.2379	benign	-0.778	Destabilizing	0.993	D	0.804	deleterious	None	None	None	None	N
T/L	0.0866	likely_benign	0.0821	benign	-0.272	Destabilizing	0.807	D	0.681	prob.neutral	None	None	None	None	N
T/M	0.0769	likely_benign	0.0761	benign	-0.023	Destabilizing	0.993	D	0.813	deleterious	None	None	None	None	N
T/N	0.2123	likely_benign	0.203	benign	-1.087	Destabilizing	0.997	D	0.766	deleterious	N	0.516012579	None	None	N
T/P	0.8726	likely_pathogenic	0.8647	pathogenic	-0.486	Destabilizing	0.997	D	0.834	deleterious	N	0.515397287	None	None	N
T/Q	0.2482	likely_benign	0.2363	benign	-1.214	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
T/R	0.2026	likely_benign	0.1818	benign	-0.645	Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
T/S	0.1535	likely_benign	0.1448	benign	-1.263	Destabilizing	0.969	D	0.613	neutral	N	0.502640637	None	None	N
T/V	0.0984	likely_benign	0.0941	benign	-0.486	Destabilizing	0.06	N	0.495	neutral	None	None	None	None	N
T/W	0.5787	likely_pathogenic	0.5473	ambiguous	-1.059	Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	N
T/Y	0.2966	likely_benign	0.2788	benign	-0.739	Destabilizing	0.998	D	0.844	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.