TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30484	91675;91676;91677	chr2:178551081;178551080;178551079	chr2:179415808;179415807;179415806
N2AB	28843	86752;86753;86754	chr2:178551081;178551080;178551079	chr2:179415808;179415807;179415806
N2A	27916	83971;83972;83973	chr2:178551081;178551080;178551079	chr2:179415808;179415807;179415806
N2B	21419	64480;64481;64482	chr2:178551081;178551080;178551079	chr2:179415808;179415807;179415806
Novex-1	21544	64855;64856;64857	chr2:178551081;178551080;178551079	chr2:179415808;179415807;179415806
Novex-2	21611	65056;65057;65058	chr2:178551081;178551080;178551079	chr2:179415808;179415807;179415806
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: Fn3-110
• Domain position: 63
• Structural Position: 94
• Q(SASA): 0.5641
• 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	rs1318850182	None	0.983	N	0.757	0.444	0.425028116352	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1318850182	None	0.983	N	0.757	0.444	0.425028116352	gnomAD-4.0.0	6.57402E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46994E-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	0.1054	likely_benign	0.1212	benign	-0.331	Destabilizing	0.63	D	0.413	neutral	N	0.480424593	None	None	N
T/C	0.4854	ambiguous	0.5739	pathogenic	-0.292	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
T/D	0.5627	ambiguous	0.6593	pathogenic	0.304	Stabilizing	0.975	D	0.712	prob.delet.	None	None	None	None	N
T/E	0.4624	ambiguous	0.5543	ambiguous	0.234	Stabilizing	0.975	D	0.716	prob.delet.	None	None	None	None	N
T/F	0.3884	ambiguous	0.4975	ambiguous	-0.817	Destabilizing	0.987	D	0.76	deleterious	None	None	None	None	N
T/G	0.2245	likely_benign	0.2722	benign	-0.462	Destabilizing	0.845	D	0.602	neutral	None	None	None	None	N
T/H	0.3523	ambiguous	0.4329	ambiguous	-0.691	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
T/I	0.3014	likely_benign	0.395	ambiguous	-0.106	Destabilizing	0.983	D	0.757	deleterious	N	0.487946238	None	None	N
T/K	0.3205	likely_benign	0.3998	ambiguous	-0.288	Destabilizing	0.967	D	0.716	prob.delet.	N	0.474922813	None	None	N
T/L	0.1446	likely_benign	0.1763	benign	-0.106	Destabilizing	0.916	D	0.609	neutral	None	None	None	None	N
T/M	0.1126	likely_benign	0.1294	benign	-0.026	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
T/N	0.1558	likely_benign	0.1884	benign	-0.105	Destabilizing	0.975	D	0.591	neutral	None	None	None	None	N
T/P	0.1449	likely_benign	0.1616	benign	-0.152	Destabilizing	0.983	D	0.759	deleterious	N	0.478930109	None	None	N
T/Q	0.2938	likely_benign	0.3483	ambiguous	-0.307	Destabilizing	0.975	D	0.764	deleterious	None	None	None	None	N
T/R	0.3153	likely_benign	0.4074	ambiguous	-0.025	Destabilizing	0.967	D	0.763	deleterious	N	0.515403998	None	None	N
T/S	0.1069	likely_benign	0.1224	benign	-0.338	Destabilizing	0.099	N	0.24	neutral	N	0.506648442	None	None	N
T/V	0.2004	likely_benign	0.259	benign	-0.152	Destabilizing	0.916	D	0.499	neutral	None	None	None	None	N
T/W	0.7262	likely_pathogenic	0.8096	pathogenic	-0.828	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
T/Y	0.414	ambiguous	0.5193	ambiguous	-0.531	Destabilizing	0.996	D	0.756	deleterious	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.