TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4632	14119;14120;14121	chr2:178739339;178739338;178739337	chr2:179604066;179604065;179604064
N2AB	4315	13168;13169;13170	chr2:178739339;178739338;178739337	chr2:179604066;179604065;179604064
N2A	None	None	chr2:None	chr2:None
N2B	4269	13030;13031;13032	chr2:178739339;178739338;178739337	chr2:179604066;179604065;179604064
Novex-1	4394	13405;13406;13407	chr2:178739339;178739338;178739337	chr2:179604066;179604065;179604064
Novex-2	4461	13606;13607;13608	chr2:178739339;178739338;178739337	chr2:179604066;179604065;179604064
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-29
• Domain position: 27
• Structural Position: 43
• Q(SASA): 0.3756
• 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
A/V	rs1225957839	-0.424	0.003	N	0.233	0.073	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
A/V	rs1225957839	-0.424	0.003	N	0.233	0.073	None	gnomAD-4.0.0	4.77392E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57437E-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
A/C	0.5759	likely_pathogenic	0.5527	ambiguous	-1.016	Destabilizing	0.973	D	0.624	neutral	None	None	None	None	N
A/D	0.7601	likely_pathogenic	0.7453	pathogenic	-1.954	Destabilizing	0.782	D	0.717	prob.delet.	N	0.508414723	None	None	N
A/E	0.6949	likely_pathogenic	0.6914	pathogenic	-1.94	Destabilizing	0.704	D	0.587	neutral	None	None	None	None	N
A/F	0.7558	likely_pathogenic	0.7459	pathogenic	-1.151	Destabilizing	0.826	D	0.757	deleterious	None	None	None	None	N
A/G	0.2303	likely_benign	0.2543	benign	-1.449	Destabilizing	0.338	N	0.571	neutral	D	0.536959657	None	None	N
A/H	0.8597	likely_pathogenic	0.8485	pathogenic	-1.712	Destabilizing	0.973	D	0.76	deleterious	None	None	None	None	N
A/I	0.4523	ambiguous	0.4569	ambiguous	-0.41	Destabilizing	0.404	N	0.628	neutral	None	None	None	None	N
A/K	0.8419	likely_pathogenic	0.8281	pathogenic	-1.425	Destabilizing	0.704	D	0.586	neutral	None	None	None	None	N
A/L	0.4901	ambiguous	0.4944	ambiguous	-0.41	Destabilizing	0.404	N	0.581	neutral	None	None	None	None	N
A/M	0.5384	ambiguous	0.5245	ambiguous	-0.253	Destabilizing	0.973	D	0.66	neutral	None	None	None	None	N
A/N	0.6916	likely_pathogenic	0.6724	pathogenic	-1.241	Destabilizing	0.704	D	0.753	deleterious	None	None	None	None	N
A/P	0.4952	ambiguous	0.5086	ambiguous	-0.612	Destabilizing	0.879	D	0.659	neutral	N	0.513042982	None	None	N
A/Q	0.7442	likely_pathogenic	0.7474	pathogenic	-1.366	Destabilizing	0.826	D	0.644	neutral	None	None	None	None	N
A/R	0.7541	likely_pathogenic	0.7467	pathogenic	-1.088	Destabilizing	0.826	D	0.657	neutral	None	None	None	None	N
A/S	0.1371	likely_benign	0.1378	benign	-1.559	Destabilizing	0.007	N	0.263	neutral	N	0.497147967	None	None	N
A/T	0.1378	likely_benign	0.1172	benign	-1.456	Destabilizing	0.003	N	0.288	neutral	N	0.508239492	None	None	N
A/V	0.1919	likely_benign	0.1898	benign	-0.612	Destabilizing	0.003	N	0.233	neutral	N	0.497302033	None	None	N
A/W	0.9477	likely_pathogenic	0.9411	pathogenic	-1.618	Destabilizing	0.991	D	0.777	deleterious	None	None	None	None	N
A/Y	0.8548	likely_pathogenic	0.8419	pathogenic	-1.198	Destabilizing	0.906	D	0.762	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.