TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31646	95161;95162;95163	chr2:178546395;178546394;178546393	chr2:179411122;179411121;179411120
N2AB	30005	90238;90239;90240	chr2:178546395;178546394;178546393	chr2:179411122;179411121;179411120
N2A	29078	87457;87458;87459	chr2:178546395;178546394;178546393	chr2:179411122;179411121;179411120
N2B	22581	67966;67967;67968	chr2:178546395;178546394;178546393	chr2:179411122;179411121;179411120
Novex-1	22706	68341;68342;68343	chr2:178546395;178546394;178546393	chr2:179411122;179411121;179411120
Novex-2	22773	68542;68543;68544	chr2:178546395;178546394;178546393	chr2:179411122;179411121;179411120
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-152
• Domain position: 26
• Structural Position: 45
• Q(SASA): 0.7802
• 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
K/T	None	None	0.543	N	0.33	0.286	0.280181792013	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.3654	ambiguous	0.3418	ambiguous	-0.109	Destabilizing	0.992	D	0.592	neutral	None	None	None	None	I
K/C	0.7325	likely_pathogenic	0.7195	pathogenic	-0.395	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
K/D	0.6471	likely_pathogenic	0.6367	pathogenic	-0.121	Destabilizing	0.999	D	0.644	neutral	None	None	None	None	I
K/E	0.2287	likely_benign	0.2041	benign	-0.041	Destabilizing	0.994	D	0.57	neutral	N	0.420560758	None	None	I
K/F	0.895	likely_pathogenic	0.8727	pathogenic	0.028	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
K/G	0.5421	ambiguous	0.5188	ambiguous	-0.397	Destabilizing	0.996	D	0.58	neutral	None	None	None	None	I
K/H	0.3642	ambiguous	0.3519	ambiguous	-0.587	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
K/I	0.5004	ambiguous	0.4589	ambiguous	0.606	Stabilizing	0.997	D	0.715	prob.delet.	N	0.492733074	None	None	I
K/L	0.4811	ambiguous	0.4596	ambiguous	0.606	Stabilizing	0.992	D	0.579	neutral	None	None	None	None	I
K/M	0.3363	likely_benign	0.3091	benign	0.081	Stabilizing	1.0	D	0.675	neutral	None	None	None	None	I
K/N	0.5273	ambiguous	0.5057	ambiguous	-0.207	Destabilizing	0.998	D	0.625	neutral	N	0.50873989	None	None	I
K/P	0.9519	likely_pathogenic	0.9402	pathogenic	0.397	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
K/Q	0.1457	likely_benign	0.1376	benign	-0.214	Destabilizing	0.999	D	0.657	neutral	N	0.495309233	None	None	I
K/R	0.0879	likely_benign	0.0855	benign	-0.305	Destabilizing	0.994	D	0.57	neutral	N	0.493482436	None	None	I
K/S	0.4641	ambiguous	0.4413	ambiguous	-0.63	Destabilizing	0.983	D	0.56	neutral	None	None	None	None	I
K/T	0.1968	likely_benign	0.1801	benign	-0.374	Destabilizing	0.543	D	0.33	neutral	N	0.413058782	None	None	I
K/V	0.3615	ambiguous	0.3286	benign	0.397	Stabilizing	0.992	D	0.578	neutral	None	None	None	None	I
K/W	0.8736	likely_pathogenic	0.8531	pathogenic	-0.017	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
K/Y	0.7745	likely_pathogenic	0.7418	pathogenic	0.298	Stabilizing	1.0	D	0.719	prob.delet.	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.