TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15054	45385;45386;45387	chr2:178621664;178621663;178621662	chr2:179486391;179486390;179486389
N2AB	13413	40462;40463;40464	chr2:178621664;178621663;178621662	chr2:179486391;179486390;179486389
N2A	12486	37681;37682;37683	chr2:178621664;178621663;178621662	chr2:179486391;179486390;179486389
N2B	5989	18190;18191;18192	chr2:178621664;178621663;178621662	chr2:179486391;179486390;179486389
Novex-1	6114	18565;18566;18567	chr2:178621664;178621663;178621662	chr2:179486391;179486390;179486389
Novex-2	6181	18766;18767;18768	chr2:178621664;178621663;178621662	chr2:179486391;179486390;179486389
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-102
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.0851
• 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/G	None	None	0.999	D	0.856	0.75	0.874876458758	gnomAD-4.0.0	1.59419E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43345E-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	0.7079	likely_pathogenic	0.6928	pathogenic	-2.4	Highly Destabilizing	0.977	D	0.581	neutral	D	0.534177785	None	None	N
V/C	0.9617	likely_pathogenic	0.9715	pathogenic	-2.306	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/D	0.9736	likely_pathogenic	0.9699	pathogenic	-3.41	Highly Destabilizing	0.999	D	0.862	deleterious	D	0.785088835	None	None	N
V/E	0.9547	likely_pathogenic	0.9517	pathogenic	-3.19	Highly Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
V/F	0.6923	likely_pathogenic	0.6924	pathogenic	-1.302	Destabilizing	0.993	D	0.845	deleterious	D	0.66754836	None	None	N
V/G	0.7464	likely_pathogenic	0.7384	pathogenic	-2.895	Highly Destabilizing	0.999	D	0.856	deleterious	D	0.711420145	None	None	N
V/H	0.9918	likely_pathogenic	0.9914	pathogenic	-2.472	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/I	0.1112	likely_benign	0.1223	benign	-0.999	Destabilizing	0.117	N	0.301	neutral	N	0.520464316	None	None	N
V/K	0.9832	likely_pathogenic	0.9836	pathogenic	-1.941	Destabilizing	0.998	D	0.856	deleterious	None	None	None	None	N
V/L	0.4697	ambiguous	0.6446	pathogenic	-0.999	Destabilizing	0.898	D	0.587	neutral	N	0.494938305	None	None	N
V/M	0.5468	ambiguous	0.5844	pathogenic	-1.38	Destabilizing	0.995	D	0.797	deleterious	None	None	None	None	N
V/N	0.9467	likely_pathogenic	0.9409	pathogenic	-2.397	Highly Destabilizing	0.999	D	0.889	deleterious	None	None	None	None	N
V/P	0.9775	likely_pathogenic	0.9795	pathogenic	-1.444	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
V/Q	0.9766	likely_pathogenic	0.9759	pathogenic	-2.235	Highly Destabilizing	0.999	D	0.888	deleterious	None	None	None	None	N
V/R	0.9745	likely_pathogenic	0.9757	pathogenic	-1.74	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
V/S	0.8867	likely_pathogenic	0.8665	pathogenic	-2.925	Highly Destabilizing	0.998	D	0.846	deleterious	None	None	None	None	N
V/T	0.7123	likely_pathogenic	0.7098	pathogenic	-2.575	Highly Destabilizing	0.983	D	0.701	prob.neutral	None	None	None	None	N
V/W	0.9945	likely_pathogenic	0.9949	pathogenic	-1.792	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/Y	0.9633	likely_pathogenic	0.9623	pathogenic	-1.535	Destabilizing	0.999	D	0.847	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.