TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4626	14101;14102;14103	chr2:178739357;178739356;178739355	chr2:179604084;179604083;179604082
N2AB	4309	13150;13151;13152	chr2:178739357;178739356;178739355	chr2:179604084;179604083;179604082
N2A	None	None	chr2:None	chr2:None
N2B	4263	13012;13013;13014	chr2:178739357;178739356;178739355	chr2:179604084;179604083;179604082
Novex-1	4388	13387;13388;13389	chr2:178739357;178739356;178739355	chr2:179604084;179604083;179604082
Novex-2	4455	13588;13589;13590	chr2:178739357;178739356;178739355	chr2:179604084;179604083;179604082
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: Ig-29
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.515
• 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
T/K	rs886039164	None	0.029	N	0.479	0.067	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/K	rs886039164	None	0.029	N	0.479	0.067	None	gnomAD-4.0.0	2.56214E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.78556E-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	0.087	likely_benign	0.0888	benign	-1.058	Destabilizing	None	N	0.247	neutral	N	0.50893731	None	None	I
T/C	0.3763	ambiguous	0.3757	ambiguous	-0.625	Destabilizing	0.356	N	0.546	neutral	None	None	None	None	I
T/D	0.3122	likely_benign	0.344	ambiguous	-0.237	Destabilizing	0.072	N	0.487	neutral	None	None	None	None	I
T/E	0.208	likely_benign	0.2158	benign	-0.227	Destabilizing	0.038	N	0.485	neutral	None	None	None	None	I
T/F	0.2061	likely_benign	0.2152	benign	-1.219	Destabilizing	0.214	N	0.593	neutral	None	None	None	None	I
T/G	0.2349	likely_benign	0.2616	benign	-1.315	Destabilizing	0.016	N	0.491	neutral	None	None	None	None	I
T/H	0.1975	likely_benign	0.2006	benign	-1.6	Destabilizing	0.356	N	0.575	neutral	None	None	None	None	I
T/I	0.1371	likely_benign	0.1432	benign	-0.458	Destabilizing	0.029	N	0.483	neutral	D	0.602563693	None	None	I
T/K	0.1286	likely_benign	0.1256	benign	-0.681	Destabilizing	0.029	N	0.479	neutral	N	0.510966168	None	None	I
T/L	0.1089	likely_benign	0.1102	benign	-0.458	Destabilizing	0.006	N	0.435	neutral	None	None	None	None	I
T/M	0.0973	likely_benign	0.092	benign	-0.059	Destabilizing	0.002	N	0.389	neutral	None	None	None	None	I
T/N	0.1211	likely_benign	0.1281	benign	-0.67	Destabilizing	0.038	N	0.395	neutral	None	None	None	None	I
T/P	0.214	likely_benign	0.2586	benign	-0.627	Destabilizing	0.055	N	0.556	neutral	D	0.584812223	None	None	I
T/Q	0.1649	likely_benign	0.1547	benign	-0.85	Destabilizing	0.002	N	0.389	neutral	None	None	None	None	I
T/R	0.1126	likely_benign	0.1068	benign	-0.469	Destabilizing	0.029	N	0.541	neutral	N	0.514371176	None	None	I
T/S	0.1064	likely_benign	0.1095	benign	-1.011	Destabilizing	None	N	0.288	neutral	N	0.485689695	None	None	I
T/V	0.1233	likely_benign	0.1261	benign	-0.627	Destabilizing	None	N	0.267	neutral	None	None	None	None	I
T/W	0.5736	likely_pathogenic	0.5699	pathogenic	-1.104	Destabilizing	0.864	D	0.609	neutral	None	None	None	None	I
T/Y	0.2533	likely_benign	0.256	benign	-0.868	Destabilizing	0.356	N	0.581	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.