TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24583	73972;73973;73974	chr2:178572385;178572384;178572383	chr2:179437112;179437111;179437110
N2AB	22942	69049;69050;69051	chr2:178572385;178572384;178572383	chr2:179437112;179437111;179437110
N2A	22015	66268;66269;66270	chr2:178572385;178572384;178572383	chr2:179437112;179437111;179437110
N2B	15518	46777;46778;46779	chr2:178572385;178572384;178572383	chr2:179437112;179437111;179437110
Novex-1	15643	47152;47153;47154	chr2:178572385;178572384;178572383	chr2:179437112;179437111;179437110
Novex-2	15710	47353;47354;47355	chr2:178572385;178572384;178572383	chr2:179437112;179437111;179437110
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-66
• Domain position: 65
• Structural Position: 97
• Q(SASA): 0.0963
• 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
L/I	None	None	0.852	D	0.833	0.659	0.799887905911	gnomAD-4.0.0	1.593E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86208E-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
L/A	0.9847	likely_pathogenic	0.9747	pathogenic	-2.625	Highly Destabilizing	0.448	N	0.658	neutral	None	None	None	None	N
L/C	0.9747	likely_pathogenic	0.9631	pathogenic	-2.315	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9996	pathogenic	-2.776	Highly Destabilizing	0.999	D	0.9	deleterious	None	None	None	None	N
L/E	0.9984	likely_pathogenic	0.9976	pathogenic	-2.627	Highly Destabilizing	0.999	D	0.892	deleterious	None	None	None	None	N
L/F	0.9472	likely_pathogenic	0.8905	pathogenic	-1.86	Destabilizing	0.998	D	0.881	deleterious	D	0.659868619	None	None	N
L/G	0.9968	likely_pathogenic	0.9953	pathogenic	-3.117	Highly Destabilizing	0.998	D	0.885	deleterious	None	None	None	None	N
L/H	0.9976	likely_pathogenic	0.9956	pathogenic	-2.428	Highly Destabilizing	1.0	D	0.876	deleterious	D	0.686213948	None	None	N
L/I	0.4507	ambiguous	0.3139	benign	-1.235	Destabilizing	0.852	D	0.833	deleterious	D	0.658859598	None	None	N
L/K	0.9974	likely_pathogenic	0.9962	pathogenic	-2.013	Highly Destabilizing	0.964	D	0.88	deleterious	None	None	None	None	N
L/M	0.6147	likely_pathogenic	0.4884	ambiguous	-1.206	Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
L/N	0.9977	likely_pathogenic	0.9967	pathogenic	-2.221	Highly Destabilizing	0.999	D	0.9	deleterious	None	None	None	None	N
L/P	0.9964	likely_pathogenic	0.9937	pathogenic	-1.676	Destabilizing	0.999	D	0.88	deleterious	D	0.686213948	None	None	N
L/Q	0.9938	likely_pathogenic	0.9897	pathogenic	-2.232	Highly Destabilizing	0.999	D	0.892	deleterious	None	None	None	None	N
L/R	0.9952	likely_pathogenic	0.9929	pathogenic	-1.528	Destabilizing	0.998	D	0.881	deleterious	D	0.660675836	None	None	N
L/S	0.998	likely_pathogenic	0.9963	pathogenic	-2.966	Highly Destabilizing	0.998	D	0.864	deleterious	None	None	None	None	N
L/T	0.9849	likely_pathogenic	0.9756	pathogenic	-2.667	Highly Destabilizing	0.996	D	0.852	deleterious	None	None	None	None	N
L/V	0.5412	ambiguous	0.3995	ambiguous	-1.676	Destabilizing	0.791	D	0.828	deleterious	D	0.608822756	None	None	N
L/W	0.9957	likely_pathogenic	0.9899	pathogenic	-2.103	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/Y	0.9961	likely_pathogenic	0.9917	pathogenic	-1.862	Destabilizing	0.996	D	0.861	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.