TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5443	16552;16553;16554	chr2:178732849;178732848;178732847	chr2:179597576;179597575;179597574
N2AB	5126	15601;15602;15603	chr2:178732849;178732848;178732847	chr2:179597576;179597575;179597574
N2A	4199	12820;12821;12822	chr2:178732849;178732848;178732847	chr2:179597576;179597575;179597574
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-37
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.3118
• 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
A/S	None	None	0.454	N	0.509	0.17	0.221734844693	gnomAD-4.0.0	2.05559E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.48821E-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
A/C	0.3993	ambiguous	0.4322	ambiguous	-1.041	Destabilizing	0.991	D	0.552	neutral	None	None	None	None	N
A/D	0.216	likely_benign	0.2859	benign	-0.598	Destabilizing	0.801	D	0.639	neutral	N	0.464871682	None	None	N
A/E	0.1801	likely_benign	0.2369	benign	-0.648	Destabilizing	0.842	D	0.544	neutral	None	None	None	None	N
A/F	0.192	likely_benign	0.2314	benign	-0.966	Destabilizing	0.949	D	0.643	neutral	None	None	None	None	N
A/G	0.1362	likely_benign	0.1518	benign	-0.977	Destabilizing	0.625	D	0.511	neutral	N	0.505622227	None	None	N
A/H	0.306	likely_benign	0.3541	ambiguous	-1.042	Destabilizing	0.998	D	0.613	neutral	None	None	None	None	N
A/I	0.1424	likely_benign	0.1719	benign	-0.307	Destabilizing	0.728	D	0.535	neutral	None	None	None	None	N
A/K	0.2738	likely_benign	0.3387	benign	-0.901	Destabilizing	0.842	D	0.536	neutral	None	None	None	None	N
A/L	0.1231	likely_benign	0.1427	benign	-0.307	Destabilizing	0.525	D	0.453	neutral	None	None	None	None	N
A/M	0.1479	likely_benign	0.1725	benign	-0.37	Destabilizing	0.325	N	0.287	neutral	None	None	None	None	N
A/N	0.1629	likely_benign	0.197	benign	-0.66	Destabilizing	0.842	D	0.642	neutral	None	None	None	None	N
A/P	0.2884	likely_benign	0.342	ambiguous	-0.414	Destabilizing	0.966	D	0.592	neutral	N	0.472299087	None	None	N
A/Q	0.2276	likely_benign	0.2599	benign	-0.823	Destabilizing	0.974	D	0.6	neutral	None	None	None	None	N
A/R	0.2479	likely_benign	0.289	benign	-0.595	Destabilizing	0.949	D	0.589	neutral	None	None	None	None	N
A/S	0.0816	likely_benign	0.0858	benign	-1.086	Destabilizing	0.454	N	0.509	neutral	N	0.410805124	None	None	N
A/T	0.0699	likely_benign	0.0764	benign	-1.027	Destabilizing	0.007	N	0.157	neutral	N	0.384119955	None	None	N
A/V	0.088	likely_benign	0.1016	benign	-0.414	Destabilizing	0.454	N	0.498	neutral	N	0.431009825	None	None	N
A/W	0.5645	likely_pathogenic	0.6328	pathogenic	-1.217	Destabilizing	0.998	D	0.648	neutral	None	None	None	None	N
A/Y	0.2881	likely_benign	0.3411	ambiguous	-0.812	Destabilizing	0.991	D	0.64	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.