TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19302	58129;58130;58131	chr2:178594590;178594589;178594588	chr2:179459317;179459316;179459315
N2AB	17661	53206;53207;53208	chr2:178594590;178594589;178594588	chr2:179459317;179459316;179459315
N2A	16734	50425;50426;50427	chr2:178594590;178594589;178594588	chr2:179459317;179459316;179459315
N2B	10237	30934;30935;30936	chr2:178594590;178594589;178594588	chr2:179459317;179459316;179459315
Novex-1	10362	31309;31310;31311	chr2:178594590;178594589;178594588	chr2:179459317;179459316;179459315
Novex-2	10429	31510;31511;31512	chr2:178594590;178594589;178594588	chr2:179459317;179459316;179459315
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-28
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1628
• 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	None	None	0.117	N	0.701	0.119	0.187945064343	gnomAD-4.0.0	1.59357E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02737E-05
T/P	rs2051000706	None	0.117	N	0.681	0.239	0.112648838833	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
T/P	rs2051000706	None	0.117	N	0.681	0.239	0.112648838833	gnomAD-4.0.0	3.8478E-06	None	None	None	None	N	None	5.07666E-05	0	None	0	0	None	0	0	0	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	0.1236	likely_benign	0.1141	benign	-1.022	Destabilizing	0.012	N	0.504	neutral	N	0.492508496	None	None	N
T/C	0.3333	likely_benign	0.3501	ambiguous	-0.986	Destabilizing	0.824	D	0.671	neutral	None	None	None	None	N
T/D	0.5189	ambiguous	0.4758	ambiguous	-1.437	Destabilizing	0.081	N	0.675	neutral	None	None	None	None	N
T/E	0.4366	ambiguous	0.4403	ambiguous	-1.321	Destabilizing	0.081	N	0.669	neutral	None	None	None	None	N
T/F	0.2906	likely_benign	0.2657	benign	-0.729	Destabilizing	0.555	D	0.669	neutral	None	None	None	None	N
T/G	0.3245	likely_benign	0.3006	benign	-1.371	Destabilizing	0.035	N	0.607	neutral	None	None	None	None	N
T/H	0.3209	likely_benign	0.3109	benign	-1.555	Destabilizing	0.555	D	0.665	neutral	None	None	None	None	N
T/I	0.1876	likely_benign	0.2069	benign	-0.143	Destabilizing	0.117	N	0.701	prob.neutral	N	0.467631481	None	None	N
T/K	0.4244	ambiguous	0.4095	ambiguous	-0.898	Destabilizing	0.081	N	0.672	neutral	None	None	None	None	N
T/L	0.158	likely_benign	0.158	benign	-0.143	Destabilizing	0.149	N	0.671	neutral	None	None	None	None	N
T/M	0.1168	likely_benign	0.1127	benign	-0.117	Destabilizing	0.791	D	0.682	prob.neutral	None	None	None	None	N
T/N	0.1784	likely_benign	0.1781	benign	-1.28	Destabilizing	0.062	N	0.673	neutral	N	0.49591416	None	None	N
T/P	0.8313	likely_pathogenic	0.7854	pathogenic	-0.404	Destabilizing	0.117	N	0.681	prob.neutral	N	0.484628102	None	None	N
T/Q	0.338	likely_benign	0.335	benign	-1.276	Destabilizing	0.38	N	0.697	prob.neutral	None	None	None	None	N
T/R	0.3993	ambiguous	0.3779	ambiguous	-0.846	Destabilizing	0.38	N	0.704	prob.neutral	None	None	None	None	N
T/S	0.1046	likely_benign	0.0976	benign	-1.46	Destabilizing	None	N	0.325	neutral	N	0.42297384	None	None	N
T/V	0.1566	likely_benign	0.1686	benign	-0.404	Destabilizing	0.149	N	0.662	neutral	None	None	None	None	N
T/W	0.6753	likely_pathogenic	0.6319	pathogenic	-0.793	Destabilizing	0.935	D	0.685	prob.neutral	None	None	None	None	N
T/Y	0.3146	likely_benign	0.3064	benign	-0.48	Destabilizing	0.555	D	0.677	prob.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.