TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6895	20908;20909;20910	chr2:178725521;178725520;178725519	chr2:179590248;179590247;179590246
N2AB	6578	19957;19958;19959	chr2:178725521;178725520;178725519	chr2:179590248;179590247;179590246
N2A	5651	17176;17177;17178	chr2:178725521;178725520;178725519	chr2:179590248;179590247;179590246
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-53
• Domain position: 42
• Structural Position: 58
• Q(SASA): 0.1125
• 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
I/S	rs2079186805	None	0.317	D	0.673	0.309	0.852700824655	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
I/S	rs2079186805	None	0.317	D	0.673	0.309	0.852700824655	gnomAD-4.0.0	6.57471E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47046E-05	0	0
I/V	rs749405543	-1.31	None	N	0.149	0.13	0.253205268125	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
I/V	rs749405543	-1.31	None	N	0.149	0.13	0.253205268125	gnomAD-4.0.0	1.59248E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86046E-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
I/A	0.4467	ambiguous	0.5901	pathogenic	-2.139	Highly Destabilizing	0.035	N	0.591	neutral	None	None	None	None	N
I/C	0.761	likely_pathogenic	0.8099	pathogenic	-1.473	Destabilizing	0.824	D	0.625	neutral	None	None	None	None	N
I/D	0.8305	likely_pathogenic	0.9473	pathogenic	-2.275	Highly Destabilizing	0.555	D	0.716	prob.delet.	None	None	None	None	N
I/E	0.7019	likely_pathogenic	0.878	pathogenic	-2.061	Highly Destabilizing	0.555	D	0.698	prob.neutral	None	None	None	None	N
I/F	0.1814	likely_benign	0.2362	benign	-1.277	Destabilizing	0.317	N	0.659	neutral	N	0.491598721	None	None	N
I/G	0.7293	likely_pathogenic	0.8693	pathogenic	-2.625	Highly Destabilizing	0.555	D	0.701	prob.neutral	None	None	None	None	N
I/H	0.6744	likely_pathogenic	0.829	pathogenic	-1.828	Destabilizing	0.935	D	0.663	neutral	None	None	None	None	N
I/K	0.5346	ambiguous	0.791	pathogenic	-1.722	Destabilizing	0.555	D	0.703	prob.neutral	None	None	None	None	N
I/L	0.1065	likely_benign	0.1093	benign	-0.754	Destabilizing	None	N	0.155	neutral	N	0.436546144	None	None	N
I/M	0.1255	likely_benign	0.1523	benign	-0.716	Destabilizing	0.317	N	0.665	neutral	N	0.498093181	None	None	N
I/N	0.4613	ambiguous	0.6982	pathogenic	-2.12	Highly Destabilizing	0.741	D	0.713	prob.delet.	N	0.499360629	None	None	N
I/P	0.6776	likely_pathogenic	0.8512	pathogenic	-1.196	Destabilizing	0.791	D	0.713	prob.delet.	None	None	None	None	N
I/Q	0.5524	ambiguous	0.7649	pathogenic	-1.982	Destabilizing	0.791	D	0.686	prob.neutral	None	None	None	None	N
I/R	0.454	ambiguous	0.7272	pathogenic	-1.451	Destabilizing	0.555	D	0.716	prob.delet.	None	None	None	None	N
I/S	0.454	ambiguous	0.658	pathogenic	-2.764	Highly Destabilizing	0.317	N	0.673	neutral	D	0.539430943	None	None	N
I/T	0.3542	ambiguous	0.5334	ambiguous	-2.399	Highly Destabilizing	0.062	N	0.601	neutral	D	0.531328748	None	None	N
I/V	0.0786	likely_benign	0.078	benign	-1.196	Destabilizing	None	N	0.149	neutral	N	0.444901842	None	None	N
I/W	0.76	likely_pathogenic	0.8578	pathogenic	-1.54	Destabilizing	0.935	D	0.678	prob.neutral	None	None	None	None	N
I/Y	0.5523	ambiguous	0.6852	pathogenic	-1.236	Destabilizing	0.555	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.