TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30114	90565;90566;90567	chr2:178552560;178552559;178552558	chr2:179417287;179417286;179417285
N2AB	28473	85642;85643;85644	chr2:178552560;178552559;178552558	chr2:179417287;179417286;179417285
N2A	27546	82861;82862;82863	chr2:178552560;178552559;178552558	chr2:179417287;179417286;179417285
N2B	21049	63370;63371;63372	chr2:178552560;178552559;178552558	chr2:179417287;179417286;179417285
Novex-1	21174	63745;63746;63747	chr2:178552560;178552559;178552558	chr2:179417287;179417286;179417285
Novex-2	21241	63946;63947;63948	chr2:178552560;178552559;178552558	chr2:179417287;179417286;179417285
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-107
• Domain position: 85
• Structural Position: 120
• Q(SASA): 0.2783
• 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
P/S	rs745525849	-1.273	None	N	0.255	0.2	0.0716867268079	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
P/S	rs745525849	-1.273	None	N	0.255	0.2	0.0716867268079	gnomAD-4.0.0	1.59133E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43279E-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
P/A	0.0543	likely_benign	0.0503	benign	-1.138	Destabilizing	None	N	0.247	neutral	N	0.486622203	None	None	I
P/C	0.2706	likely_benign	0.2762	benign	-0.611	Destabilizing	None	N	0.511	neutral	None	None	None	None	I
P/D	0.4169	ambiguous	0.3278	benign	-0.596	Destabilizing	0.004	N	0.448	neutral	None	None	None	None	I
P/E	0.3406	ambiguous	0.2592	benign	-0.616	Destabilizing	0.004	N	0.452	neutral	None	None	None	None	I
P/F	0.3221	likely_benign	0.2957	benign	-0.892	Destabilizing	None	N	0.46	neutral	None	None	None	None	I
P/G	0.1326	likely_benign	0.112	benign	-1.419	Destabilizing	None	N	0.307	neutral	None	None	None	None	I
P/H	0.2222	likely_benign	0.2109	benign	-0.891	Destabilizing	0.103	N	0.58	neutral	N	0.516642649	None	None	I
P/I	0.3519	ambiguous	0.2714	benign	-0.487	Destabilizing	0.009	N	0.483	neutral	None	None	None	None	I
P/K	0.4062	ambiguous	0.3296	benign	-0.809	Destabilizing	0.004	N	0.451	neutral	None	None	None	None	I
P/L	0.2551	likely_benign	0.1759	benign	-0.487	Destabilizing	0.001	N	0.493	neutral	N	0.521109193	None	None	I
P/M	0.321	likely_benign	0.2649	benign	-0.372	Destabilizing	0.132	N	0.608	neutral	None	None	None	None	I
P/N	0.3064	likely_benign	0.2604	benign	-0.554	Destabilizing	0.004	N	0.467	neutral	None	None	None	None	I
P/Q	0.2496	likely_benign	0.1988	benign	-0.719	Destabilizing	0.021	N	0.543	neutral	None	None	None	None	I
P/R	0.3332	likely_benign	0.2449	benign	-0.325	Destabilizing	0.007	N	0.55	neutral	D	0.533732946	None	None	I
P/S	0.0975	likely_benign	0.0941	benign	-1.076	Destabilizing	None	N	0.255	neutral	N	0.503511917	None	None	I
P/T	0.1244	likely_benign	0.1013	benign	-0.986	Destabilizing	0.001	N	0.378	neutral	D	0.533986435	None	None	I
P/V	0.2285	likely_benign	0.1743	benign	-0.668	Destabilizing	0.002	N	0.446	neutral	None	None	None	None	I
P/W	0.5249	ambiguous	0.4871	ambiguous	-1.05	Destabilizing	None	N	0.513	neutral	None	None	None	None	I
P/Y	0.3055	likely_benign	0.2871	benign	-0.745	Destabilizing	0.004	N	0.499	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.