TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6169	18730;18731;18732	chr2:178729748;178729747;178729746	chr2:179594475;179594474;179594473
N2AB	5852	17779;17780;17781	chr2:178729748;178729747;178729746	chr2:179594475;179594474;179594473
N2A	4925	14998;14999;15000	chr2:178729748;178729747;178729746	chr2:179594475;179594474;179594473
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: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-45
• Domain position: 65
• Structural Position: 145
• Q(SASA): 0.449
• 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
R/G	None	None	0.425	N	0.375	0.3	0.492267288202	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
R/K	None	None	0.002	N	0.159	0.147	0.221019684889	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85848E-06	0	0
R/T	None	None	0.642	N	0.339	0.275	0.516715673709	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85848E-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
R/A	0.1156	likely_benign	0.1311	benign	-0.229	Destabilizing	0.495	N	0.354	neutral	None	None	None	None	N
R/C	0.1471	likely_benign	0.1525	benign	-0.174	Destabilizing	0.995	D	0.267	neutral	None	None	None	None	N
R/D	0.2212	likely_benign	0.2263	benign	0.049	Stabilizing	0.003	N	0.178	neutral	None	None	None	None	N
R/E	0.1366	likely_benign	0.145	benign	0.129	Stabilizing	0.013	N	0.146	neutral	None	None	None	None	N
R/F	0.2624	likely_benign	0.2812	benign	-0.336	Destabilizing	0.944	D	0.275	neutral	None	None	None	None	N
R/G	0.0796	likely_benign	0.0928	benign	-0.47	Destabilizing	0.425	N	0.375	neutral	N	0.440168026	None	None	N
R/H	0.0842	likely_benign	0.0882	benign	-0.933	Destabilizing	0.007	N	0.248	neutral	None	None	None	None	N
R/I	0.1268	likely_benign	0.1281	benign	0.386	Stabilizing	0.944	D	0.298	neutral	None	None	None	None	N
R/K	0.0702	likely_benign	0.0719	benign	-0.191	Destabilizing	0.002	N	0.159	neutral	N	0.455153334	None	None	N
R/L	0.1101	likely_benign	0.1184	benign	0.386	Stabilizing	0.704	D	0.345	neutral	None	None	None	None	N
R/M	0.117	likely_benign	0.1231	benign	0.057	Stabilizing	0.975	D	0.291	neutral	N	0.495637306	None	None	N
R/N	0.1892	likely_benign	0.1976	benign	0.241	Stabilizing	0.543	D	0.215	neutral	None	None	None	None	N
R/P	0.3523	ambiguous	0.4028	ambiguous	0.202	Stabilizing	0.828	D	0.311	neutral	None	None	None	None	N
R/Q	0.0745	likely_benign	0.0793	benign	0.067	Stabilizing	0.704	D	0.245	neutral	None	None	None	None	N
R/S	0.1303	likely_benign	0.1443	benign	-0.298	Destabilizing	0.425	N	0.339	neutral	N	0.407882249	None	None	N
R/T	0.0788	likely_benign	0.082	benign	-0.065	Destabilizing	0.642	D	0.339	neutral	N	0.39855069	None	None	N
R/V	0.1483	likely_benign	0.149	benign	0.202	Stabilizing	0.828	D	0.341	neutral	None	None	None	None	N
R/W	0.1148	likely_benign	0.1228	benign	-0.237	Destabilizing	0.993	D	0.31	neutral	D	0.533424904	None	None	N
R/Y	0.2178	likely_benign	0.229	benign	0.14	Stabilizing	0.893	D	0.286	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.