TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8456	25591;25592;25593	chr2:178717368;178717367;178717366	chr2:179582095;179582094;179582093
N2AB	8139	24640;24641;24642	chr2:178717368;178717367;178717366	chr2:179582095;179582094;179582093
N2A	7212	21859;21860;21861	chr2:178717368;178717367;178717366	chr2:179582095;179582094;179582093
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-70
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1247
• 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
P/L	rs1308450887	None	0.992	D	0.757	0.733	0.834275830499	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/L	rs1308450887	None	0.992	D	0.757	0.733	0.834275830499	gnomAD-4.0.0	6.57099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47011E-05	0	0
P/R	None	None	0.631	D	0.674	0.693	0.663271509172	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
P/T	None	None	0.936	D	0.689	0.69	0.676758004843	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.7181	likely_pathogenic	0.6969	pathogenic	-1.33	Destabilizing	0.799	D	0.664	neutral	D	0.632567861	None	None	N
P/C	0.9862	likely_pathogenic	0.9798	pathogenic	-1.088	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/D	0.9988	likely_pathogenic	0.9982	pathogenic	-1.106	Destabilizing	0.861	D	0.717	prob.delet.	None	None	None	None	N
P/E	0.9968	likely_pathogenic	0.9955	pathogenic	-1.149	Destabilizing	0.831	D	0.689	prob.neutral	None	None	None	None	N
P/F	0.9986	likely_pathogenic	0.9974	pathogenic	-1.269	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/G	0.9838	likely_pathogenic	0.9764	pathogenic	-1.584	Destabilizing	0.984	D	0.731	prob.delet.	None	None	None	None	N
P/H	0.9957	likely_pathogenic	0.9924	pathogenic	-1.129	Destabilizing	1.0	D	0.797	deleterious	D	0.649192635	None	None	N
P/I	0.9707	likely_pathogenic	0.9606	pathogenic	-0.754	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
P/K	0.9983	likely_pathogenic	0.9975	pathogenic	-0.956	Destabilizing	0.994	D	0.695	prob.neutral	None	None	None	None	N
P/L	0.9212	likely_pathogenic	0.892	pathogenic	-0.754	Destabilizing	0.992	D	0.757	deleterious	D	0.63297147	None	None	N
P/M	0.9918	likely_pathogenic	0.988	pathogenic	-0.621	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
P/N	0.9977	likely_pathogenic	0.9961	pathogenic	-0.735	Destabilizing	0.993	D	0.767	deleterious	None	None	None	None	N
P/Q	0.9929	likely_pathogenic	0.9894	pathogenic	-0.988	Destabilizing	0.914	D	0.673	neutral	None	None	None	None	N
P/R	0.9911	likely_pathogenic	0.9866	pathogenic	-0.461	Destabilizing	0.631	D	0.674	neutral	D	0.649192635	None	None	N
P/S	0.9626	likely_pathogenic	0.9477	pathogenic	-1.248	Destabilizing	0.856	D	0.624	neutral	D	0.632769665	None	None	N
P/T	0.9586	likely_pathogenic	0.9456	pathogenic	-1.186	Destabilizing	0.936	D	0.689	prob.neutral	D	0.648990831	None	None	N
P/V	0.9176	likely_pathogenic	0.8921	pathogenic	-0.912	Destabilizing	0.63	D	0.661	neutral	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9991	pathogenic	-1.36	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/Y	0.9989	likely_pathogenic	0.9979	pathogenic	-1.054	Destabilizing	1.0	D	0.818	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.