TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6911	20956;20957;20958	chr2:178725473;178725472;178725471	chr2:179590200;179590199;179590198
N2AB	6594	20005;20006;20007	chr2:178725473;178725472;178725471	chr2:179590200;179590199;179590198
N2A	5667	17224;17225;17226	chr2:178725473;178725472;178725471	chr2:179590200;179590199;179590198
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-53
• Domain position: 58
• Structural Position: 137
• Q(SASA): 0.2168
• 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/A	None	None	0.996	N	0.454	0.511	0.489728331402	gnomAD-4.0.0	1.59258E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02663E-05
T/P	None	None	1.0	D	0.752	0.686	0.581280949539	gnomAD-4.0.0	3.18516E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72076E-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	0.0858	likely_benign	0.0846	benign	-1.118	Destabilizing	0.996	D	0.454	neutral	N	0.521148187	None	None	N
T/C	0.3819	ambiguous	0.3507	ambiguous	-0.956	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
T/D	0.6736	likely_pathogenic	0.6573	pathogenic	-1.89	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
T/E	0.4188	ambiguous	0.4171	ambiguous	-1.682	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
T/F	0.2233	likely_benign	0.1947	benign	-0.694	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
T/G	0.3307	likely_benign	0.3231	benign	-1.531	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
T/H	0.2424	likely_benign	0.2255	benign	-1.71	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
T/I	0.1558	likely_benign	0.1389	benign	-0.03	Destabilizing	0.998	D	0.679	prob.neutral	N	0.504564869	None	None	N
T/K	0.1712	likely_benign	0.1696	benign	-0.736	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
T/L	0.1092	likely_benign	0.1005	benign	-0.03	Destabilizing	0.994	D	0.491	neutral	None	None	None	None	N
T/M	0.1026	likely_benign	0.0975	benign	-0.155	Destabilizing	0.985	D	0.431	neutral	None	None	None	None	N
T/N	0.2067	likely_benign	0.1967	benign	-1.473	Destabilizing	1.0	D	0.664	neutral	N	0.521908655	None	None	N
T/P	0.8386	likely_pathogenic	0.8579	pathogenic	-0.362	Destabilizing	1.0	D	0.752	deleterious	D	0.534025429	None	None	N
T/Q	0.2302	likely_benign	0.226	benign	-1.194	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
T/R	0.136	likely_benign	0.1336	benign	-0.982	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
T/S	0.1311	likely_benign	0.1231	benign	-1.595	Destabilizing	0.998	D	0.443	neutral	N	0.479977208	None	None	N
T/V	0.1165	likely_benign	0.1105	benign	-0.362	Destabilizing	0.994	D	0.443	neutral	None	None	None	None	N
T/W	0.6157	likely_pathogenic	0.5867	pathogenic	-0.965	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
T/Y	0.2789	likely_benign	0.2567	benign	-0.558	Destabilizing	1.0	D	0.819	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.