TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28850	86773;86774;86775	chr2:178559584;178559583;178559582	chr2:179424311;179424310;179424309
N2AB	27209	81850;81851;81852	chr2:178559584;178559583;178559582	chr2:179424311;179424310;179424309
N2A	26282	79069;79070;79071	chr2:178559584;178559583;178559582	chr2:179424311;179424310;179424309
N2B	19785	59578;59579;59580	chr2:178559584;178559583;178559582	chr2:179424311;179424310;179424309
Novex-1	19910	59953;59954;59955	chr2:178559584;178559583;178559582	chr2:179424311;179424310;179424309
Novex-2	19977	60154;60155;60156	chr2:178559584;178559583;178559582	chr2:179424311;179424310;179424309
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-98
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2613
• 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/N	rs377049333	None	0.007	N	0.275	0.105	None	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
T/A	0.052	likely_benign	0.0512	benign	-0.657	Destabilizing	None	N	0.057	neutral	N	0.421512402	None	None	N
T/C	0.1609	likely_benign	0.1606	benign	-0.362	Destabilizing	0.245	N	0.398	neutral	None	None	None	None	N
T/D	0.2386	likely_benign	0.2184	benign	-0.545	Destabilizing	0.018	N	0.39	neutral	None	None	None	None	N
T/E	0.1777	likely_benign	0.1589	benign	-0.536	Destabilizing	0.018	N	0.457	neutral	None	None	None	None	N
T/F	0.1496	likely_benign	0.1405	benign	-0.627	Destabilizing	0.085	N	0.513	neutral	None	None	None	None	N
T/G	0.0898	likely_benign	0.0884	benign	-0.94	Destabilizing	None	N	0.203	neutral	None	None	None	None	N
T/H	0.1573	likely_benign	0.1463	benign	-1.309	Destabilizing	0.245	N	0.463	neutral	None	None	None	None	N
T/I	0.0863	likely_benign	0.0828	benign	0.009	Stabilizing	0.007	N	0.402	neutral	N	0.499493183	None	None	N
T/K	0.1178	likely_benign	0.1038	benign	-0.889	Destabilizing	0.009	N	0.429	neutral	None	None	None	None	N
T/L	0.0627	likely_benign	0.0618	benign	0.009	Stabilizing	0.004	N	0.311	neutral	None	None	None	None	N
T/M	0.0734	likely_benign	0.073	benign	0.301	Stabilizing	0.245	N	0.399	neutral	None	None	None	None	N
T/N	0.0817	likely_benign	0.0828	benign	-0.812	Destabilizing	0.007	N	0.275	neutral	N	0.517385511	None	None	N
T/P	0.1793	likely_benign	0.1631	benign	-0.18	Destabilizing	0.033	N	0.434	neutral	N	0.487756037	None	None	N
T/Q	0.1285	likely_benign	0.1187	benign	-0.936	Destabilizing	0.044	N	0.46	neutral	None	None	None	None	N
T/R	0.1093	likely_benign	0.0932	benign	-0.692	Destabilizing	0.044	N	0.439	neutral	None	None	None	None	N
T/S	0.0701	likely_benign	0.0696	benign	-0.998	Destabilizing	None	N	0.055	neutral	N	0.436652426	None	None	N
T/V	0.0722	likely_benign	0.0687	benign	-0.18	Destabilizing	None	N	0.06	neutral	None	None	None	None	N
T/W	0.4114	ambiguous	0.3739	ambiguous	-0.636	Destabilizing	0.788	D	0.44	neutral	None	None	None	None	N
T/Y	0.1678	likely_benign	0.1592	benign	-0.408	Destabilizing	0.085	N	0.508	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.