TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32627	98104;98105;98106	chr2:178540287;178540286;178540285	chr2:179405014;179405013;179405012
N2AB	30986	93181;93182;93183	chr2:178540287;178540286;178540285	chr2:179405014;179405013;179405012
N2A	30059	90400;90401;90402	chr2:178540287;178540286;178540285	chr2:179405014;179405013;179405012
N2B	23562	70909;70910;70911	chr2:178540287;178540286;178540285	chr2:179405014;179405013;179405012
Novex-1	23687	71284;71285;71286	chr2:178540287;178540286;178540285	chr2:179405014;179405013;179405012
Novex-2	23754	71485;71486;71487	chr2:178540287;178540286;178540285	chr2:179405014;179405013;179405012
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-126
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.3636
• 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
E/D	None	None	0.999	N	0.479	0.22	0.336892272479	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	0	0	0
E/K	None	None	0.999	N	0.652	0.429	0.373357554552	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
E/A	0.1998	likely_benign	0.2139	benign	-0.58	Destabilizing	0.999	D	0.677	prob.neutral	N	0.44192496	None	None	N
E/C	0.8404	likely_pathogenic	0.847	pathogenic	-0.194	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
E/D	0.1607	likely_benign	0.1508	benign	-1.106	Destabilizing	0.999	D	0.479	neutral	N	0.314496793	None	None	N
E/F	0.8356	likely_pathogenic	0.8582	pathogenic	-0.628	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
E/G	0.2518	likely_benign	0.2869	benign	-0.89	Destabilizing	1.0	D	0.671	neutral	N	0.478789837	None	None	N
E/H	0.6599	likely_pathogenic	0.6948	pathogenic	-1.008	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
E/I	0.4976	ambiguous	0.5332	ambiguous	0.24	Stabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/K	0.2594	likely_benign	0.3411	ambiguous	-0.241	Destabilizing	0.999	D	0.652	neutral	N	0.47488274	None	None	N
E/L	0.5601	ambiguous	0.5988	pathogenic	0.24	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
E/M	0.5725	likely_pathogenic	0.6124	pathogenic	0.708	Stabilizing	1.0	D	0.616	neutral	None	None	None	None	N
E/N	0.3454	ambiguous	0.3427	ambiguous	-0.585	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/P	0.5793	likely_pathogenic	0.5963	pathogenic	-0.011	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/Q	0.2375	likely_benign	0.2684	benign	-0.499	Destabilizing	1.0	D	0.629	neutral	N	0.4843103	None	None	N
E/R	0.4133	ambiguous	0.4909	ambiguous	-0.258	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/S	0.2705	likely_benign	0.2798	benign	-0.857	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
E/T	0.2577	likely_benign	0.2748	benign	-0.593	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/V	0.2965	likely_benign	0.331	benign	-0.011	Destabilizing	1.0	D	0.719	prob.delet.	N	0.475229457	None	None	N
E/W	0.9474	likely_pathogenic	0.9565	pathogenic	-0.582	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
E/Y	0.7353	likely_pathogenic	0.7674	pathogenic	-0.396	Destabilizing	1.0	D	0.661	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.