TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25918	77977;77978;77979	chr2:178568380;178568379;178568378	chr2:179433107;179433106;179433105
N2AB	24277	73054;73055;73056	chr2:178568380;178568379;178568378	chr2:179433107;179433106;179433105
N2A	23350	70273;70274;70275	chr2:178568380;178568379;178568378	chr2:179433107;179433106;179433105
N2B	16853	50782;50783;50784	chr2:178568380;178568379;178568378	chr2:179433107;179433106;179433105
Novex-1	16978	51157;51158;51159	chr2:178568380;178568379;178568378	chr2:179433107;179433106;179433105
Novex-2	17045	51358;51359;51360	chr2:178568380;178568379;178568378	chr2:179433107;179433106;179433105
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-76
• Domain position: 29
• Structural Position: 30
• Q(SASA): 0.2897
• Predicted PPI site: I

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	rs1484655947	-0.185	0.994	N	0.69	0.395	0.388970301349	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
T/I	rs1484655947	-0.185	0.994	N	0.69	0.395	0.388970301349	gnomAD-4.0.0	1.64272E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.06921E-05	0	1.65772E-05
T/R	None	None	0.994	N	0.697	0.402	0.527857482506	gnomAD-4.0.0	6.84466E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99658E-07	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	0.1233	likely_benign	0.1393	benign	-1.018	Destabilizing	0.958	D	0.489	neutral	N	0.512747695	None	None	I
T/C	0.6286	likely_pathogenic	0.6501	pathogenic	-0.677	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	I
T/D	0.2365	likely_benign	0.2196	benign	-0.896	Destabilizing	0.086	N	0.341	neutral	None	None	None	None	I
T/E	0.3796	ambiguous	0.4255	ambiguous	-0.826	Destabilizing	0.938	D	0.512	neutral	None	None	None	None	I
T/F	0.4985	ambiguous	0.5518	ambiguous	-0.881	Destabilizing	0.998	D	0.726	prob.delet.	None	None	None	None	I
T/G	0.2962	likely_benign	0.3077	benign	-1.349	Destabilizing	0.968	D	0.604	neutral	None	None	None	None	I
T/H	0.3557	ambiguous	0.3907	ambiguous	-1.618	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
T/I	0.4321	ambiguous	0.4835	ambiguous	-0.201	Destabilizing	0.994	D	0.69	prob.neutral	N	0.487386352	None	None	I
T/K	0.3292	likely_benign	0.3921	ambiguous	-0.863	Destabilizing	0.988	D	0.582	neutral	N	0.4725341	None	None	I
T/L	0.1616	likely_benign	0.1849	benign	-0.201	Destabilizing	0.984	D	0.544	neutral	None	None	None	None	I
T/M	0.1421	likely_benign	0.1606	benign	0.093	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	I
T/N	0.1143	likely_benign	0.1081	benign	-1.058	Destabilizing	0.982	D	0.621	neutral	None	None	None	None	I
T/P	0.2129	likely_benign	0.2046	benign	-0.441	Destabilizing	0.994	D	0.689	prob.neutral	N	0.50924603	None	None	I
T/Q	0.3284	likely_benign	0.3703	ambiguous	-1.122	Destabilizing	0.995	D	0.707	prob.neutral	None	None	None	None	I
T/R	0.3095	likely_benign	0.3644	ambiguous	-0.746	Destabilizing	0.994	D	0.697	prob.neutral	N	0.483005033	None	None	I
T/S	0.1082	likely_benign	0.1064	benign	-1.297	Destabilizing	0.958	D	0.463	neutral	N	0.501933269	None	None	I
T/V	0.2878	likely_benign	0.3104	benign	-0.441	Destabilizing	0.984	D	0.535	neutral	None	None	None	None	I
T/W	0.7966	likely_pathogenic	0.8241	pathogenic	-0.873	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
T/Y	0.4752	ambiguous	0.52	ambiguous	-0.61	Destabilizing	0.998	D	0.724	prob.delet.	None	None	None	None	I

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.