TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16183	48772;48773;48774	chr2:178615398;178615397;178615396	chr2:179480125;179480124;179480123
N2AB	14542	43849;43850;43851	chr2:178615398;178615397;178615396	chr2:179480125;179480124;179480123
N2A	13615	41068;41069;41070	chr2:178615398;178615397;178615396	chr2:179480125;179480124;179480123
N2B	7118	21577;21578;21579	chr2:178615398;178615397;178615396	chr2:179480125;179480124;179480123
Novex-1	7243	21952;21953;21954	chr2:178615398;178615397;178615396	chr2:179480125;179480124;179480123
Novex-2	7310	22153;22154;22155	chr2:178615398;178615397;178615396	chr2:179480125;179480124;179480123
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-5
• Domain position: 29
• Structural Position: 31
• Q(SASA): 0.3738
• 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
G/D	rs2057147235	None	1.0	D	0.848	0.572	0.412458657427	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/D	rs2057147235	None	1.0	D	0.848	0.572	0.412458657427	gnomAD-4.0.0	6.58467E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47254E-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
G/A	0.9284	likely_pathogenic	0.9235	pathogenic	-0.36	Destabilizing	1.0	D	0.727	prob.delet.	D	0.70383522	None	None	I
G/C	0.974	likely_pathogenic	0.9729	pathogenic	-0.806	Destabilizing	1.0	D	0.795	deleterious	D	0.752418866	None	None	I
G/D	0.9946	likely_pathogenic	0.9933	pathogenic	-0.794	Destabilizing	1.0	D	0.848	deleterious	D	0.702497091	None	None	I
G/E	0.9964	likely_pathogenic	0.9959	pathogenic	-0.961	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
G/F	0.9965	likely_pathogenic	0.9962	pathogenic	-1.195	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
G/H	0.9955	likely_pathogenic	0.9957	pathogenic	-0.68	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/I	0.9975	likely_pathogenic	0.9968	pathogenic	-0.478	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
G/K	0.9957	likely_pathogenic	0.9951	pathogenic	-0.788	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
G/L	0.9959	likely_pathogenic	0.9955	pathogenic	-0.478	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/M	0.998	likely_pathogenic	0.9979	pathogenic	-0.321	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
G/N	0.9894	likely_pathogenic	0.9915	pathogenic	-0.408	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
G/P	0.9994	likely_pathogenic	0.999	pathogenic	-0.405	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/Q	0.9941	likely_pathogenic	0.9941	pathogenic	-0.743	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
G/R	0.9832	likely_pathogenic	0.9808	pathogenic	-0.321	Destabilizing	1.0	D	0.838	deleterious	D	0.629343584	None	None	I
G/S	0.9127	likely_pathogenic	0.9132	pathogenic	-0.537	Destabilizing	1.0	D	0.807	deleterious	D	0.676345323	None	None	I
G/T	0.9906	likely_pathogenic	0.9891	pathogenic	-0.641	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	I
G/V	0.9947	likely_pathogenic	0.9935	pathogenic	-0.405	Destabilizing	1.0	D	0.819	deleterious	D	0.69536983	None	None	I
G/W	0.9928	likely_pathogenic	0.9917	pathogenic	-1.344	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/Y	0.995	likely_pathogenic	0.9946	pathogenic	-0.981	Destabilizing	1.0	D	0.79	deleterious	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.