TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18768	56527;56528;56529	chr2:178599599;178599598;178599597	chr2:179464326;179464325;179464324
N2AB	17127	51604;51605;51606	chr2:178599599;178599598;178599597	chr2:179464326;179464325;179464324
N2A	16200	48823;48824;48825	chr2:178599599;178599598;178599597	chr2:179464326;179464325;179464324
N2B	9703	29332;29333;29334	chr2:178599599;178599598;178599597	chr2:179464326;179464325;179464324
Novex-1	9828	29707;29708;29709	chr2:178599599;178599598;178599597	chr2:179464326;179464325;179464324
Novex-2	9895	29908;29909;29910	chr2:178599599;178599598;178599597	chr2:179464326;179464325;179464324
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-116
• Domain position: 81
• Structural Position: 161
• Q(SASA): 0.1672
• 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
N/S	None	None	0.999	N	0.581	0.622	0.289847578895	gnomAD-4.0.0	1.62068E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.91026E-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
N/A	0.9916	likely_pathogenic	0.9886	pathogenic	-0.779	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
N/C	0.8992	likely_pathogenic	0.8879	pathogenic	None	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
N/D	0.9765	likely_pathogenic	0.9664	pathogenic	-0.87	Destabilizing	0.999	D	0.619	neutral	D	0.540738066	None	None	I
N/E	0.9971	likely_pathogenic	0.995	pathogenic	-0.84	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
N/F	0.9992	likely_pathogenic	0.9988	pathogenic	-0.897	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
N/G	0.971	likely_pathogenic	0.9602	pathogenic	-1.033	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	I
N/H	0.9659	likely_pathogenic	0.9515	pathogenic	-1.017	Destabilizing	1.0	D	0.751	deleterious	D	0.542005513	None	None	I
N/I	0.9936	likely_pathogenic	0.9907	pathogenic	-0.164	Destabilizing	1.0	D	0.719	prob.delet.	D	0.530902698	None	None	I
N/K	0.9985	likely_pathogenic	0.9973	pathogenic	-0.231	Destabilizing	1.0	D	0.729	prob.delet.	D	0.541498534	None	None	I
N/L	0.9793	likely_pathogenic	0.9735	pathogenic	-0.164	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
N/M	0.9919	likely_pathogenic	0.9889	pathogenic	0.48	Stabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
N/P	0.9958	likely_pathogenic	0.9943	pathogenic	-0.342	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
N/Q	0.9964	likely_pathogenic	0.9938	pathogenic	-0.984	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
N/R	0.9967	likely_pathogenic	0.9941	pathogenic	-0.124	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
N/S	0.6243	likely_pathogenic	0.612	pathogenic	-0.706	Destabilizing	0.999	D	0.581	neutral	N	0.486069679	None	None	I
N/T	0.924	likely_pathogenic	0.9105	pathogenic	-0.52	Destabilizing	0.999	D	0.703	prob.neutral	N	0.51811436	None	None	I
N/V	0.99	likely_pathogenic	0.9868	pathogenic	-0.342	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
N/W	0.9995	likely_pathogenic	0.9991	pathogenic	-0.713	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
N/Y	0.9928	likely_pathogenic	0.9896	pathogenic	-0.476	Destabilizing	1.0	D	0.739	prob.delet.	D	0.542005513	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.