TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35728	107407;107408;107409	chr2:178528569;178528568;178528567	chr2:179393296;179393295;179393294
N2AB	34087	102484;102485;102486	chr2:178528569;178528568;178528567	chr2:179393296;179393295;179393294
N2A	33160	99703;99704;99705	chr2:178528569;178528568;178528567	chr2:179393296;179393295;179393294
N2B	26663	80212;80213;80214	chr2:178528569;178528568;178528567	chr2:179393296;179393295;179393294
Novex-1	26788	80587;80588;80589	chr2:178528569;178528568;178528567	chr2:179393296;179393295;179393294
Novex-2	26855	80788;80789;80790	chr2:178528569;178528568;178528567	chr2:179393296;179393295;179393294
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-168
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.6941
• 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
E/K	rs764891218	0.76	0.852	N	0.506	0.309	None	gnomAD-2.1.1	1.8E-05	None	None	None	None	I	None	4.16E-05	0	None	0	0	None	0	None	0	3.14E-05	0
E/K	rs764891218	0.76	0.852	N	0.506	0.309	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs764891218	0.76	0.852	N	0.506	0.309	None	gnomAD-4.0.0	1.48877E-05	None	None	None	None	I	None	1.33572E-05	0	None	0	2.22965E-05	None	0	3.28839E-04	1.44213E-05	0	4.80708E-05

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
E/A	0.2781	likely_benign	0.3127	benign	-0.054	Destabilizing	0.505	D	0.562	neutral	N	0.434780849	None	None	I
E/C	0.939	likely_pathogenic	0.9647	pathogenic	-0.105	Destabilizing	0.991	D	0.679	prob.neutral	None	None	None	None	I
E/D	0.2546	likely_benign	0.2686	benign	-0.319	Destabilizing	None	N	0.257	neutral	N	0.390067279	None	None	I
E/F	0.7715	likely_pathogenic	0.8016	pathogenic	-0.042	Destabilizing	0.967	D	0.617	neutral	None	None	None	None	I
E/G	0.395	ambiguous	0.4393	ambiguous	-0.184	Destabilizing	0.505	D	0.603	neutral	N	0.502160634	None	None	I
E/H	0.6352	likely_pathogenic	0.6868	pathogenic	0.517	Stabilizing	0.967	D	0.476	neutral	None	None	None	None	I
E/I	0.4172	ambiguous	0.4484	ambiguous	0.233	Stabilizing	0.906	D	0.613	neutral	None	None	None	None	I
E/K	0.201	likely_benign	0.2359	benign	0.519	Stabilizing	0.852	D	0.506	neutral	N	0.456694916	None	None	I
E/L	0.5472	ambiguous	0.5919	pathogenic	0.233	Stabilizing	0.906	D	0.591	neutral	None	None	None	None	I
E/M	0.539	ambiguous	0.5809	pathogenic	0.072	Stabilizing	0.991	D	0.621	neutral	None	None	None	None	I
E/N	0.3678	ambiguous	0.391	ambiguous	0.184	Stabilizing	0.404	N	0.511	neutral	None	None	None	None	I
E/P	0.9328	likely_pathogenic	0.9421	pathogenic	0.156	Stabilizing	0.906	D	0.507	neutral	None	None	None	None	I
E/Q	0.1978	likely_benign	0.2193	benign	0.21	Stabilizing	0.722	D	0.469	neutral	N	0.474627316	None	None	I
E/R	0.3939	ambiguous	0.443	ambiguous	0.733	Stabilizing	0.826	D	0.48	neutral	None	None	None	None	I
E/S	0.2997	likely_benign	0.3228	benign	0.07	Stabilizing	0.404	N	0.497	neutral	None	None	None	None	I
E/T	0.3422	ambiguous	0.3792	ambiguous	0.189	Stabilizing	0.575	D	0.537	neutral	None	None	None	None	I
E/V	0.2889	likely_benign	0.3192	benign	0.156	Stabilizing	0.879	D	0.559	neutral	N	0.449056868	None	None	I
E/W	0.9496	likely_pathogenic	0.9612	pathogenic	0.031	Stabilizing	0.991	D	0.685	prob.neutral	None	None	None	None	I
E/Y	0.7023	likely_pathogenic	0.7393	pathogenic	0.194	Stabilizing	0.967	D	0.599	neutral	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.