TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18188	54787;54788;54789	chr2:178604125;178604124;178604123	chr2:179468852;179468851;179468850
N2AB	16547	49864;49865;49866	chr2:178604125;178604124;178604123	chr2:179468852;179468851;179468850
N2A	15620	47083;47084;47085	chr2:178604125;178604124;178604123	chr2:179468852;179468851;179468850
N2B	9123	27592;27593;27594	chr2:178604125;178604124;178604123	chr2:179468852;179468851;179468850
Novex-1	9248	27967;27968;27969	chr2:178604125;178604124;178604123	chr2:179468852;179468851;179468850
Novex-2	9315	28168;28169;28170	chr2:178604125;178604124;178604123	chr2:179468852;179468851;179468850
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: Fn3-20
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.3376
• 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
T/I	None	None	0.966	N	0.586	0.276	0.453401982733	gnomAD-4.0.0	1.59411E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88352E-05	0	0	0	0
T/N	None	None	0.801	N	0.419	0.172	0.346085882481	gnomAD-4.0.0	1.59411E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86395E-06	0	0
T/S	None	None	0.625	N	0.443	0.104	0.203808441222	gnomAD-4.0.0	1.59411E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86395E-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	0.0871	likely_benign	0.0785	benign	-0.99	Destabilizing	0.625	D	0.403	neutral	N	0.419338889	None	None	N
T/C	0.4279	ambiguous	0.4123	ambiguous	-0.684	Destabilizing	0.998	D	0.528	neutral	None	None	None	None	N
T/D	0.2219	likely_benign	0.1922	benign	-0.255	Destabilizing	0.525	D	0.426	neutral	None	None	None	None	N
T/E	0.155	likely_benign	0.1274	benign	-0.204	Destabilizing	0.002	N	0.247	neutral	None	None	None	None	N
T/F	0.2491	likely_benign	0.1838	benign	-0.97	Destabilizing	0.991	D	0.581	neutral	None	None	None	None	N
T/G	0.1973	likely_benign	0.196	benign	-1.296	Destabilizing	0.842	D	0.496	neutral	None	None	None	None	N
T/H	0.258	likely_benign	0.1972	benign	-1.531	Destabilizing	0.974	D	0.568	neutral	None	None	None	None	N
T/I	0.1542	likely_benign	0.1261	benign	-0.248	Destabilizing	0.966	D	0.586	neutral	N	0.469420992	None	None	N
T/K	0.1851	likely_benign	0.1479	benign	-0.734	Destabilizing	0.525	D	0.451	neutral	None	None	None	None	N
T/L	0.084	likely_benign	0.0718	benign	-0.248	Destabilizing	0.842	D	0.456	neutral	None	None	None	None	N
T/M	0.096	likely_benign	0.0788	benign	-0.073	Destabilizing	0.991	D	0.547	neutral	None	None	None	None	N
T/N	0.0908	likely_benign	0.0761	benign	-0.832	Destabilizing	0.801	D	0.419	neutral	N	0.450603158	None	None	N
T/P	0.1103	likely_benign	0.1147	benign	-0.462	Destabilizing	0.891	D	0.557	neutral	N	0.489796264	None	None	N
T/Q	0.1573	likely_benign	0.1276	benign	-0.878	Destabilizing	0.08	N	0.212	neutral	None	None	None	None	N
T/R	0.2252	likely_benign	0.1682	benign	-0.626	Destabilizing	0.842	D	0.487	neutral	None	None	None	None	N
T/S	0.0951	likely_benign	0.0881	benign	-1.152	Destabilizing	0.625	D	0.443	neutral	N	0.432900045	None	None	N
T/V	0.1203	likely_benign	0.1051	benign	-0.462	Destabilizing	0.915	D	0.436	neutral	None	None	None	None	N
T/W	0.6124	likely_pathogenic	0.5436	ambiguous	-0.912	Destabilizing	0.998	D	0.581	neutral	None	None	None	None	N
T/Y	0.2588	likely_benign	0.2056	benign	-0.661	Destabilizing	0.991	D	0.579	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.