TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14203	42832;42833;42834	chr2:178633892;178633891;178633890	chr2:179498619;179498618;179498617
N2AB	12562	37909;37910;37911	chr2:178633892;178633891;178633890	chr2:179498619;179498618;179498617
N2A	11635	35128;35129;35130	chr2:178633892;178633891;178633890	chr2:179498619;179498618;179498617
N2B	5138	15637;15638;15639	chr2:178633892;178633891;178633890	chr2:179498619;179498618;179498617
Novex-1	5263	16012;16013;16014	chr2:178633892;178633891;178633890	chr2:179498619;179498618;179498617
Novex-2	5330	16213;16214;16215	chr2:178633892;178633891;178633890	chr2:179498619;179498618;179498617
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-92
• Domain position: 62
• Structural Position: 144
• Q(SASA): 0.0977
• 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
V/M	rs761861743	-1.278	0.638	D	0.591	0.456	0.693830937314	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/M	rs761861743	-1.278	0.638	D	0.591	0.456	0.693830937314	gnomAD-4.0.0	1.592E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	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
V/A	0.6774	likely_pathogenic	0.6666	pathogenic	-1.868	Destabilizing	0.094	N	0.532	neutral	N	0.513027114	None	None	N
V/C	0.9453	likely_pathogenic	0.9474	pathogenic	-1.894	Destabilizing	0.947	D	0.654	neutral	None	None	None	None	N
V/D	0.9852	likely_pathogenic	0.9896	pathogenic	-3.1	Highly Destabilizing	0.7	D	0.753	deleterious	None	None	None	None	N
V/E	0.9748	likely_pathogenic	0.9808	pathogenic	-3.04	Highly Destabilizing	0.638	D	0.711	prob.delet.	D	0.69058275	None	None	N
V/F	0.8555	likely_pathogenic	0.875	pathogenic	-1.4	Destabilizing	0.7	D	0.706	prob.neutral	None	None	None	None	N
V/G	0.7736	likely_pathogenic	0.7911	pathogenic	-2.218	Highly Destabilizing	0.638	D	0.729	prob.delet.	D	0.69058275	None	None	N
V/H	0.9943	likely_pathogenic	0.9956	pathogenic	-1.682	Destabilizing	0.982	D	0.733	prob.delet.	None	None	None	None	N
V/I	0.1472	likely_benign	0.1435	benign	-0.955	Destabilizing	0.121	N	0.534	neutral	None	None	None	None	N
V/K	0.9758	likely_pathogenic	0.9832	pathogenic	-1.672	Destabilizing	0.7	D	0.709	prob.delet.	None	None	None	None	N
V/L	0.5158	ambiguous	0.5244	ambiguous	-0.955	Destabilizing	0.002	N	0.327	neutral	D	0.523363222	None	None	N
V/M	0.5812	likely_pathogenic	0.5934	pathogenic	-1.012	Destabilizing	0.638	D	0.591	neutral	D	0.689505241	None	None	N
V/N	0.9484	likely_pathogenic	0.9588	pathogenic	-1.847	Destabilizing	0.7	D	0.745	deleterious	None	None	None	None	N
V/P	0.9575	likely_pathogenic	0.9792	pathogenic	-1.232	Destabilizing	0.826	D	0.716	prob.delet.	None	None	None	None	N
V/Q	0.9788	likely_pathogenic	0.9836	pathogenic	-2.004	Highly Destabilizing	0.826	D	0.708	prob.delet.	None	None	None	None	N
V/R	0.9677	likely_pathogenic	0.9766	pathogenic	-1.159	Destabilizing	0.7	D	0.747	deleterious	None	None	None	None	N
V/S	0.9154	likely_pathogenic	0.9154	pathogenic	-2.261	Highly Destabilizing	0.539	D	0.695	prob.neutral	None	None	None	None	N
V/T	0.7499	likely_pathogenic	0.7467	pathogenic	-2.097	Highly Destabilizing	0.002	N	0.389	neutral	None	None	None	None	N
V/W	0.9971	likely_pathogenic	0.9979	pathogenic	-1.713	Destabilizing	0.982	D	0.715	prob.delet.	None	None	None	None	N
V/Y	0.9823	likely_pathogenic	0.9867	pathogenic	-1.408	Destabilizing	0.826	D	0.679	prob.neutral	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.