TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30632	92119;92120;92121	chr2:178549828;178549827;178549826	chr2:179414555;179414554;179414553
N2AB	28991	87196;87197;87198	chr2:178549828;178549827;178549826	chr2:179414555;179414554;179414553
N2A	28064	84415;84416;84417	chr2:178549828;178549827;178549826	chr2:179414555;179414554;179414553
N2B	21567	64924;64925;64926	chr2:178549828;178549827;178549826	chr2:179414555;179414554;179414553
Novex-1	21692	65299;65300;65301	chr2:178549828;178549827;178549826	chr2:179414555;179414554;179414553
Novex-2	21759	65500;65501;65502	chr2:178549828;178549827;178549826	chr2:179414555;179414554;179414553
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: Fn3-111
• Domain position: 14
• Structural Position: 15
• Q(SASA): 0.1286
• 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	rs1698611582	None	1.0	N	0.756	0.496	0.763475692304	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/S	rs1698611582	None	1.0	N	0.756	0.496	0.763475692304	gnomAD-4.0.0	6.57315E-06	None	None	None	None	N	None	2.41336E-05	0	None	0	0	None	0	0	0	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	0.5268	ambiguous	0.6136	pathogenic	-2.177	Highly Destabilizing	0.999	D	0.503	neutral	None	None	None	None	N
I/C	0.7183	likely_pathogenic	0.7721	pathogenic	-1.838	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
I/D	0.8752	likely_pathogenic	0.9213	pathogenic	-2.355	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
I/E	0.7648	likely_pathogenic	0.8205	pathogenic	-2.304	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
I/F	0.2762	likely_benign	0.3826	ambiguous	-1.637	Destabilizing	1.0	D	0.705	prob.neutral	N	0.480375368	None	None	N
I/G	0.8137	likely_pathogenic	0.8701	pathogenic	-2.547	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
I/H	0.7018	likely_pathogenic	0.7726	pathogenic	-1.767	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
I/K	0.446	ambiguous	0.5147	ambiguous	-1.581	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
I/L	0.1537	likely_benign	0.1931	benign	-1.187	Destabilizing	0.993	D	0.309	neutral	N	0.480579348	None	None	N
I/M	0.1316	likely_benign	0.1614	benign	-1.12	Destabilizing	1.0	D	0.724	prob.delet.	D	0.525063631	None	None	N
I/N	0.4814	ambiguous	0.5573	ambiguous	-1.597	Destabilizing	1.0	D	0.837	deleterious	N	0.49514826	None	None	N
I/P	0.8357	likely_pathogenic	0.8858	pathogenic	-1.491	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
I/Q	0.5959	likely_pathogenic	0.6692	pathogenic	-1.781	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
I/R	0.3878	ambiguous	0.4652	ambiguous	-1.001	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
I/S	0.5268	ambiguous	0.5967	pathogenic	-2.226	Highly Destabilizing	1.0	D	0.756	deleterious	N	0.481412098	None	None	N
I/T	0.3323	likely_benign	0.3859	ambiguous	-2.054	Highly Destabilizing	1.0	D	0.681	prob.neutral	D	0.52429284	None	None	N
I/V	0.0718	likely_benign	0.0793	benign	-1.491	Destabilizing	0.993	D	0.312	neutral	N	0.385858246	None	None	N
I/W	0.8901	likely_pathogenic	0.9333	pathogenic	-1.76	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
I/Y	0.6786	likely_pathogenic	0.7563	pathogenic	-1.516	Destabilizing	1.0	D	0.798	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.