TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17419	52480;52481;52482	chr2:178608756;178608755;178608754	chr2:179473483;179473482;179473481
N2AB	15778	47557;47558;47559	chr2:178608756;178608755;178608754	chr2:179473483;179473482;179473481
N2A	14851	44776;44777;44778	chr2:178608756;178608755;178608754	chr2:179473483;179473482;179473481
N2B	8354	25285;25286;25287	chr2:178608756;178608755;178608754	chr2:179473483;179473482;179473481
Novex-1	8479	25660;25661;25662	chr2:178608756;178608755;178608754	chr2:179473483;179473482;179473481
Novex-2	8546	25861;25862;25863	chr2:178608756;178608755;178608754	chr2:179473483;179473482;179473481
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-14
• Domain position: 51
• Structural Position: 66
• Q(SASA): 0.4504
• 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
I/T	rs1162756483	-1.05	0.012	N	0.306	0.087	0.678712887374	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	4.14E-05	0	None	0	0	None	0	None	0	1.56E-05	0
I/T	rs1162756483	-1.05	0.012	N	0.306	0.087	0.678712887374	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs1162756483	-1.05	0.012	N	0.306	0.087	0.678712887374	gnomAD-4.0.0	5.58129E-06	None	None	None	None	I	None	2.67265E-05	0	None	0	2.24225E-05	None	0	0	5.08807E-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
I/A	0.2762	likely_benign	0.2899	benign	-1.273	Destabilizing	0.007	N	0.296	neutral	None	None	None	None	I
I/C	0.6376	likely_pathogenic	0.6538	pathogenic	-0.788	Destabilizing	0.356	N	0.334	neutral	None	None	None	None	I
I/D	0.7246	likely_pathogenic	0.7268	pathogenic	-0.665	Destabilizing	None	N	0.367	neutral	None	None	None	None	I
I/E	0.5614	ambiguous	0.5713	pathogenic	-0.663	Destabilizing	0.038	N	0.323	neutral	None	None	None	None	I
I/F	0.2019	likely_benign	0.2102	benign	-0.768	Destabilizing	0.171	N	0.311	neutral	N	0.4797312	None	None	I
I/G	0.5936	likely_pathogenic	0.5977	pathogenic	-1.567	Destabilizing	0.072	N	0.339	neutral	None	None	None	None	I
I/H	0.4795	ambiguous	0.4906	ambiguous	-0.636	Destabilizing	0.628	D	0.359	neutral	None	None	None	None	I
I/K	0.4782	ambiguous	0.478	ambiguous	-0.878	Destabilizing	0.072	N	0.339	neutral	None	None	None	None	I
I/L	0.1254	likely_benign	0.1367	benign	-0.554	Destabilizing	0.002	N	0.175	neutral	N	0.480480561	None	None	I
I/M	0.074	likely_benign	0.0823	benign	-0.523	Destabilizing	0.002	N	0.179	neutral	N	0.505032289	None	None	I
I/N	0.2356	likely_benign	0.2447	benign	-0.785	Destabilizing	0.029	N	0.385	neutral	N	0.511667473	None	None	I
I/P	0.9336	likely_pathogenic	0.9261	pathogenic	-0.762	Destabilizing	0.356	N	0.409	neutral	None	None	None	None	I
I/Q	0.3849	ambiguous	0.4143	ambiguous	-0.932	Destabilizing	0.214	N	0.407	neutral	None	None	None	None	I
I/R	0.4098	ambiguous	0.4097	ambiguous	-0.282	Destabilizing	0.214	N	0.405	neutral	None	None	None	None	I
I/S	0.265	likely_benign	0.2695	benign	-1.357	Destabilizing	0.001	N	0.283	neutral	N	0.476248177	None	None	I
I/T	0.1759	likely_benign	0.1816	benign	-1.24	Destabilizing	0.012	N	0.306	neutral	N	0.447618781	None	None	I
I/V	0.0877	likely_benign	0.0905	benign	-0.762	Destabilizing	None	N	0.151	neutral	N	0.430129098	None	None	I
I/W	0.7528	likely_pathogenic	0.7588	pathogenic	-0.838	Destabilizing	0.864	D	0.389	neutral	None	None	None	None	I
I/Y	0.5124	ambiguous	0.5301	ambiguous	-0.611	Destabilizing	0.356	N	0.367	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.