TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2177	6754;6755;6756	chr2:178775182;178775181;178775180	chr2:179639909;179639908;179639907
N2AB	2177	6754;6755;6756	chr2:178775182;178775181;178775180	chr2:179639909;179639908;179639907
N2A	2177	6754;6755;6756	chr2:178775182;178775181;178775180	chr2:179639909;179639908;179639907
N2B	2131	6616;6617;6618	chr2:178775182;178775181;178775180	chr2:179639909;179639908;179639907
Novex-1	2131	6616;6617;6618	chr2:178775182;178775181;178775180	chr2:179639909;179639908;179639907
Novex-2	2131	6616;6617;6618	chr2:178775182;178775181;178775180	chr2:179639909;179639908;179639907
Novex-3	2177	6754;6755;6756	chr2:178775182;178775181;178775180	chr2:179639909;179639908;179639907

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-11
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3909
• 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	0.018	N	0.266	0.298	0.405700215632	gnomAD-4.0.0	2.05244E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79866E-06	1.15931E-05	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	0.1189	likely_benign	0.1236	benign	-0.783	Destabilizing	0.856	D	0.423	neutral	D	0.574332437	None	None	N
T/C	0.5152	ambiguous	0.5365	ambiguous	-0.419	Destabilizing	0.998	D	0.607	neutral	None	None	None	None	N
T/D	0.5125	ambiguous	0.5436	ambiguous	-0.258	Destabilizing	0.994	D	0.643	neutral	None	None	None	None	N
T/E	0.3737	ambiguous	0.4024	ambiguous	-0.301	Destabilizing	0.994	D	0.639	neutral	None	None	None	None	N
T/F	0.2555	likely_benign	0.2727	benign	-1.07	Destabilizing	0.965	D	0.685	prob.neutral	None	None	None	None	N
T/G	0.3181	likely_benign	0.3279	benign	-0.979	Destabilizing	0.994	D	0.642	neutral	None	None	None	None	N
T/H	0.2629	likely_benign	0.2829	benign	-1.266	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
T/I	0.1141	likely_benign	0.1234	benign	-0.363	Destabilizing	0.018	N	0.266	neutral	N	0.505351467	None	None	N
T/K	0.2212	likely_benign	0.2428	benign	-0.627	Destabilizing	0.977	D	0.645	neutral	N	0.503210427	None	None	N
T/L	0.0845	likely_benign	0.0895	benign	-0.363	Destabilizing	0.62	D	0.465	neutral	None	None	None	None	N
T/M	0.0974	likely_benign	0.099	benign	0.082	Stabilizing	0.991	D	0.616	neutral	None	None	None	None	N
T/N	0.1421	likely_benign	0.1499	benign	-0.48	Destabilizing	0.994	D	0.585	neutral	None	None	None	None	N
T/P	0.3099	likely_benign	0.3289	benign	-0.473	Destabilizing	0.992	D	0.625	neutral	D	0.681598655	None	None	N
T/Q	0.2294	likely_benign	0.2437	benign	-0.774	Destabilizing	0.994	D	0.627	neutral	None	None	None	None	N
T/R	0.1893	likely_benign	0.2095	benign	-0.268	Destabilizing	0.992	D	0.617	neutral	N	0.504336304	None	None	N
T/S	0.1192	likely_benign	0.1211	benign	-0.751	Destabilizing	0.924	D	0.417	neutral	D	0.534028764	None	None	N
T/V	0.121	likely_benign	0.1262	benign	-0.473	Destabilizing	0.62	D	0.391	neutral	None	None	None	None	N
T/W	0.6794	likely_pathogenic	0.707	pathogenic	-0.967	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
T/Y	0.3676	ambiguous	0.3936	ambiguous	-0.737	Destabilizing	0.994	D	0.695	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.