TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9714	29365;29366;29367	chr2:178706734;178706733;178706732	chr2:179571461;179571460;179571459
N2AB	9397	28414;28415;28416	chr2:178706734;178706733;178706732	chr2:179571461;179571460;179571459
N2A	8470	25633;25634;25635	chr2:178706734;178706733;178706732	chr2:179571461;179571460;179571459
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-83
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.4541
• 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
T/A	None	None	0.103	None	0.173	0.1	0.132336055621	gnomAD-4.0.0	1.60692E-06	None	None	None	None	I	None	0	0	None	4.81371E-05	0	None	0	0	0	0	0
T/P	None	None	0.984	None	0.527	0.33	0.250579442822	gnomAD-4.0.0	1.60692E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.88319E-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
T/A	0.1433	likely_benign	0.099	benign	-0.721	Destabilizing	0.103	N	0.173	neutral	None	None	None	None	I
T/C	0.767	likely_pathogenic	0.616	pathogenic	-0.448	Destabilizing	0.999	D	0.558	neutral	None	None	None	None	I
T/D	0.7767	likely_pathogenic	0.6096	pathogenic	-0.65	Destabilizing	0.988	D	0.501	neutral	None	None	None	None	I
T/E	0.6287	likely_pathogenic	0.4575	ambiguous	-0.679	Destabilizing	0.988	D	0.483	neutral	None	None	None	None	I
T/F	0.6454	likely_pathogenic	0.3989	ambiguous	-0.958	Destabilizing	0.988	D	0.631	neutral	None	None	None	None	I
T/G	0.6366	likely_pathogenic	0.4376	ambiguous	-0.939	Destabilizing	0.919	D	0.489	neutral	None	None	None	None	I
T/H	0.6038	likely_pathogenic	0.426	ambiguous	-1.282	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
T/I	0.2825	likely_benign	0.1805	benign	-0.237	Destabilizing	0.211	N	0.241	neutral	None	None	None	None	I
T/K	0.416	ambiguous	0.2782	benign	-0.738	Destabilizing	0.988	D	0.483	neutral	None	None	None	None	I
T/L	0.259	likely_benign	0.1519	benign	-0.237	Destabilizing	0.702	D	0.427	neutral	None	None	None	None	I
T/M	0.1589	likely_benign	0.1095	benign	0.225	Stabilizing	0.988	D	0.557	neutral	None	None	None	None	I
T/N	0.3671	ambiguous	0.2251	benign	-0.665	Destabilizing	0.995	D	0.471	neutral	None	None	None	None	I
T/P	0.3581	ambiguous	0.2138	benign	-0.368	Destabilizing	0.984	D	0.527	neutral	None	None	None	None	I
T/Q	0.4878	ambiguous	0.3431	ambiguous	-0.96	Destabilizing	0.996	D	0.544	neutral	None	None	None	None	I
T/R	0.373	ambiguous	0.2156	benign	-0.386	Destabilizing	0.988	D	0.546	neutral	None	None	None	None	I
T/S	0.2562	likely_benign	0.1681	benign	-0.869	Destabilizing	0.811	D	0.382	neutral	None	None	None	None	I
T/V	0.1784	likely_benign	0.1319	benign	-0.368	Destabilizing	0.034	N	0.181	neutral	None	None	None	None	I
T/W	0.8922	likely_pathogenic	0.7599	pathogenic	-0.89	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
T/Y	0.7201	likely_pathogenic	0.4941	ambiguous	-0.644	Destabilizing	0.996	D	0.635	neutral	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.