TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24171	72736;72737;72738	chr2:178573621;178573620;178573619	chr2:179438348;179438347;179438346
N2AB	22530	67813;67814;67815	chr2:178573621;178573620;178573619	chr2:179438348;179438347;179438346
N2A	21603	65032;65033;65034	chr2:178573621;178573620;178573619	chr2:179438348;179438347;179438346
N2B	15106	45541;45542;45543	chr2:178573621;178573620;178573619	chr2:179438348;179438347;179438346
Novex-1	15231	45916;45917;45918	chr2:178573621;178573620;178573619	chr2:179438348;179438347;179438346
Novex-2	15298	46117;46118;46119	chr2:178573621;178573620;178573619	chr2:179438348;179438347;179438346
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-63
• Domain position: 50
• Structural Position: 66
• Q(SASA): 0.5245
• 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	rs1365291247	None	0.998	N	0.691	0.419	0.44770609447	gnomAD-4.0.0	5.83419E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.01046E-05	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	0.2685	likely_benign	0.3338	benign	-0.658	Destabilizing	0.825	D	0.501	neutral	N	0.506512369	None	None	N
T/C	0.773	likely_pathogenic	0.8576	pathogenic	-0.408	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
T/D	0.9141	likely_pathogenic	0.9433	pathogenic	0.165	Stabilizing	0.991	D	0.647	neutral	None	None	None	None	N
T/E	0.8554	likely_pathogenic	0.9059	pathogenic	0.139	Stabilizing	0.995	D	0.654	neutral	None	None	None	None	N
T/F	0.7764	likely_pathogenic	0.8515	pathogenic	-0.836	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
T/G	0.6215	likely_pathogenic	0.6794	pathogenic	-0.876	Destabilizing	0.086	N	0.339	neutral	None	None	None	None	N
T/H	0.7411	likely_pathogenic	0.8191	pathogenic	-1.066	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
T/I	0.5398	ambiguous	0.6109	pathogenic	-0.184	Destabilizing	0.998	D	0.691	prob.neutral	N	0.497335525	None	None	N
T/K	0.8177	likely_pathogenic	0.8531	pathogenic	-0.565	Destabilizing	0.988	D	0.663	neutral	N	0.513822343	None	None	N
T/L	0.3575	ambiguous	0.4379	ambiguous	-0.184	Destabilizing	0.984	D	0.603	neutral	None	None	None	None	N
T/M	0.1939	likely_benign	0.2448	benign	-0.038	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
T/N	0.3657	ambiguous	0.4313	ambiguous	-0.415	Destabilizing	0.991	D	0.635	neutral	None	None	None	None	N
T/P	0.8331	likely_pathogenic	0.8379	pathogenic	-0.31	Destabilizing	0.998	D	0.69	prob.neutral	D	0.523719767	None	None	N
T/Q	0.649	likely_pathogenic	0.7233	pathogenic	-0.583	Destabilizing	0.998	D	0.705	prob.neutral	None	None	None	None	N
T/R	0.7561	likely_pathogenic	0.8162	pathogenic	-0.29	Destabilizing	0.994	D	0.695	prob.neutral	N	0.514497134	None	None	N
T/S	0.3228	likely_benign	0.405	ambiguous	-0.71	Destabilizing	0.958	D	0.493	neutral	N	0.520500387	None	None	N
T/V	0.3612	ambiguous	0.4405	ambiguous	-0.31	Destabilizing	0.984	D	0.576	neutral	None	None	None	None	N
T/W	0.9301	likely_pathogenic	0.9535	pathogenic	-0.782	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
T/Y	0.8012	likely_pathogenic	0.8751	pathogenic	-0.545	Destabilizing	0.998	D	0.712	prob.delet.	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.