TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2474	7645;7646;7647	chr2:178773636;178773635;178773634	chr2:179638363;179638362;179638361
N2AB	2474	7645;7646;7647	chr2:178773636;178773635;178773634	chr2:179638363;179638362;179638361
N2A	2474	7645;7646;7647	chr2:178773636;178773635;178773634	chr2:179638363;179638362;179638361
N2B	2428	7507;7508;7509	chr2:178773636;178773635;178773634	chr2:179638363;179638362;179638361
Novex-1	2428	7507;7508;7509	chr2:178773636;178773635;178773634	chr2:179638363;179638362;179638361
Novex-2	2428	7507;7508;7509	chr2:178773636;178773635;178773634	chr2:179638363;179638362;179638361
Novex-3	2474	7645;7646;7647	chr2:178773636;178773635;178773634	chr2:179638363;179638362;179638361

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-14
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.8308
• Predicted PPI site: I

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/S	rs750891001	-0.038	None	N	0.118	0.067	0.143124449307	gnomAD-2.1.1	3.99E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.83E-06	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	0.0965	likely_benign	0.0933	benign	-0.167	Destabilizing	None	N	0.116	neutral	N	0.412745142	None	None	I
T/C	0.4915	ambiguous	0.4635	ambiguous	-0.56	Destabilizing	0.667	D	0.381	neutral	None	None	None	None	I
T/D	0.5309	ambiguous	0.5177	ambiguous	-0.112	Destabilizing	0.22	N	0.341	neutral	None	None	None	None	I
T/E	0.5045	ambiguous	0.4902	ambiguous	-0.2	Destabilizing	0.055	N	0.305	neutral	None	None	None	None	I
T/F	0.3931	ambiguous	0.3616	ambiguous	-0.866	Destabilizing	0.667	D	0.387	neutral	None	None	None	None	I
T/G	0.2516	likely_benign	0.2403	benign	-0.2	Destabilizing	0.055	N	0.239	neutral	None	None	None	None	I
T/H	0.3485	ambiguous	0.3341	benign	-0.29	Destabilizing	0.667	D	0.342	neutral	None	None	None	None	I
T/I	0.2943	likely_benign	0.2756	benign	-0.199	Destabilizing	0.003	N	0.217	neutral	N	0.507691084	None	None	I
T/K	0.3602	ambiguous	0.3626	ambiguous	-0.363	Destabilizing	0.055	N	0.312	neutral	None	None	None	None	I
T/L	0.1441	likely_benign	0.1365	benign	-0.199	Destabilizing	0.055	N	0.259	neutral	None	None	None	None	I
T/M	0.1306	likely_benign	0.1212	benign	-0.32	Destabilizing	0.667	D	0.378	neutral	None	None	None	None	I
T/N	0.142	likely_benign	0.1371	benign	-0.271	Destabilizing	0.096	N	0.279	neutral	D	0.548972229	None	None	I
T/P	0.1183	likely_benign	0.1183	benign	-0.167	Destabilizing	0.301	N	0.427	neutral	N	0.358164047	None	None	I
T/Q	0.325	likely_benign	0.3197	benign	-0.431	Destabilizing	0.22	N	0.429	neutral	None	None	None	None	I
T/R	0.3401	ambiguous	0.334	benign	-0.087	Destabilizing	0.001	N	0.214	neutral	None	None	None	None	I
T/S	0.1037	likely_benign	0.1007	benign	-0.409	Destabilizing	None	N	0.118	neutral	N	0.471936404	None	None	I
T/V	0.2088	likely_benign	0.196	benign	-0.167	Destabilizing	0.055	N	0.227	neutral	None	None	None	None	I
T/W	0.7672	likely_pathogenic	0.746	pathogenic	-0.984	Destabilizing	0.958	D	0.327	neutral	None	None	None	None	I
T/Y	0.4117	ambiguous	0.3958	ambiguous	-0.656	Destabilizing	0.667	D	0.369	neutral	None	None	None	None	I

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.