TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21429	64510;64511;64512	chr2:178586616;178586615;178586614	chr2:179451343;179451342;179451341
N2AB	19788	59587;59588;59589	chr2:178586616;178586615;178586614	chr2:179451343;179451342;179451341
N2A	18861	56806;56807;56808	chr2:178586616;178586615;178586614	chr2:179451343;179451342;179451341
N2B	12364	37315;37316;37317	chr2:178586616;178586615;178586614	chr2:179451343;179451342;179451341
Novex-1	12489	37690;37691;37692	chr2:178586616;178586615;178586614	chr2:179451343;179451342;179451341
Novex-2	12556	37891;37892;37893	chr2:178586616;178586615;178586614	chr2:179451343;179451342;179451341
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: Fn3-43
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.3502
• 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	rs1276697618	-0.238	0.012	N	0.401	0.102	0.208000267992	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14837E-04	0	None	0	0	None	0	None	0	0	0
T/I	rs1276697618	-0.238	0.012	N	0.401	0.102	0.208000267992	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1276697618	-0.238	0.012	N	0.401	0.102	0.208000267992	gnomAD-4.0.0	2.56412E-06	None	None	None	None	N	None	3.38547E-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	0.0753	likely_benign	0.0843	benign	-0.801	Destabilizing	None	N	0.108	neutral	N	0.442831824	None	None	N
T/C	0.3249	likely_benign	0.4138	ambiguous	-0.482	Destabilizing	0.356	N	0.483	neutral	None	None	None	None	N
T/D	0.3875	ambiguous	0.4239	ambiguous	0.416	Stabilizing	0.016	N	0.423	neutral	None	None	None	None	N
T/E	0.3094	likely_benign	0.3039	benign	0.41	Stabilizing	0.016	N	0.387	neutral	None	None	None	None	N
T/F	0.2689	likely_benign	0.3049	benign	-1.066	Destabilizing	0.356	N	0.59	neutral	None	None	None	None	N
T/G	0.1715	likely_benign	0.2293	benign	-1.016	Destabilizing	0.016	N	0.343	neutral	None	None	None	None	N
T/H	0.243	likely_benign	0.2715	benign	-1.131	Destabilizing	None	N	0.312	neutral	None	None	None	None	N
T/I	0.1702	likely_benign	0.1746	benign	-0.329	Destabilizing	0.012	N	0.401	neutral	N	0.502688204	None	None	N
T/K	0.2218	likely_benign	0.2046	benign	-0.417	Destabilizing	0.016	N	0.418	neutral	None	None	None	None	N
T/L	0.1031	likely_benign	0.1078	benign	-0.329	Destabilizing	0.016	N	0.356	neutral	None	None	None	None	N
T/M	0.0965	likely_benign	0.0989	benign	-0.214	Destabilizing	0.356	N	0.495	neutral	None	None	None	None	N
T/N	0.1224	likely_benign	0.1357	benign	-0.375	Destabilizing	None	N	0.14	neutral	N	0.45399018	None	None	N
T/P	0.1087	likely_benign	0.1368	benign	-0.455	Destabilizing	0.055	N	0.491	neutral	N	0.474000093	None	None	N
T/Q	0.2292	likely_benign	0.2335	benign	-0.468	Destabilizing	0.072	N	0.525	neutral	None	None	None	None	N
T/R	0.2285	likely_benign	0.2162	benign	-0.21	Destabilizing	0.072	N	0.445	neutral	None	None	None	None	N
T/S	0.0923	likely_benign	0.1065	benign	-0.731	Destabilizing	None	N	0.148	neutral	N	0.421531045	None	None	N
T/V	0.1151	likely_benign	0.1132	benign	-0.455	Destabilizing	None	N	0.113	neutral	None	None	None	None	N
T/W	0.5708	likely_pathogenic	0.6431	pathogenic	-1.009	Destabilizing	0.864	D	0.508	neutral	None	None	None	None	N
T/Y	0.286	likely_benign	0.3311	benign	-0.748	Destabilizing	0.12	N	0.588	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.