TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5713	17362;17363;17364	chr2:178731738;178731737;178731736	chr2:179596465;179596464;179596463
N2AB	5396	16411;16412;16413	chr2:178731738;178731737;178731736	chr2:179596465;179596464;179596463
N2A	4469	13630;13631;13632	chr2:178731738;178731737;178731736	chr2:179596465;179596464;179596463
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-40
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1536
• 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
N/S	rs374597389	None	0.001	N	0.302	0.323	0.126345400529	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/S	rs374597389	None	0.001	N	0.302	0.323	0.126345400529	gnomAD-4.0.0	2.0299E-06	None	None	None	None	I	None	3.49455E-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
N/A	0.9818	likely_pathogenic	0.9731	pathogenic	-0.93	Destabilizing	0.157	N	0.579	neutral	None	None	None	None	I
N/C	0.9586	likely_pathogenic	0.947	pathogenic	-0.199	Destabilizing	0.909	D	0.744	deleterious	None	None	None	None	I
N/D	0.9193	likely_pathogenic	0.8935	pathogenic	-1.029	Destabilizing	0.124	N	0.598	neutral	D	0.540738066	None	None	I
N/E	0.9932	likely_pathogenic	0.9903	pathogenic	-0.92	Destabilizing	0.157	N	0.619	neutral	None	None	None	None	I
N/F	0.9992	likely_pathogenic	0.9987	pathogenic	-0.647	Destabilizing	0.726	D	0.736	prob.delet.	None	None	None	None	I
N/G	0.9421	likely_pathogenic	0.9236	pathogenic	-1.271	Destabilizing	0.157	N	0.541	neutral	None	None	None	None	I
N/H	0.9539	likely_pathogenic	0.9323	pathogenic	-1.008	Destabilizing	0.667	D	0.614	neutral	D	0.542005513	None	None	I
N/I	0.9943	likely_pathogenic	0.9897	pathogenic	-0.056	Destabilizing	0.009	N	0.523	neutral	D	0.542259003	None	None	I
N/K	0.9954	likely_pathogenic	0.9932	pathogenic	-0.35	Destabilizing	0.124	N	0.619	neutral	D	0.530142229	None	None	I
N/L	0.9782	likely_pathogenic	0.9675	pathogenic	-0.056	Destabilizing	0.157	N	0.659	neutral	None	None	None	None	I
N/M	0.9898	likely_pathogenic	0.9827	pathogenic	0.388	Stabilizing	0.909	D	0.713	prob.delet.	None	None	None	None	I
N/P	0.9923	likely_pathogenic	0.9895	pathogenic	-0.319	Destabilizing	0.567	D	0.721	prob.delet.	None	None	None	None	I
N/Q	0.9944	likely_pathogenic	0.9919	pathogenic	-1.023	Destabilizing	0.567	D	0.659	neutral	None	None	None	None	I
N/R	0.9915	likely_pathogenic	0.9892	pathogenic	-0.36	Destabilizing	0.567	D	0.663	neutral	None	None	None	None	I
N/S	0.5145	ambiguous	0.4575	ambiguous	-1.001	Destabilizing	0.001	N	0.302	neutral	N	0.49643848	None	None	I
N/T	0.9006	likely_pathogenic	0.8543	pathogenic	-0.71	Destabilizing	0.124	N	0.576	neutral	N	0.518278945	None	None	I
N/V	0.9869	likely_pathogenic	0.978	pathogenic	-0.319	Destabilizing	0.157	N	0.68	prob.neutral	None	None	None	None	I
N/W	0.9994	likely_pathogenic	0.9992	pathogenic	-0.399	Destabilizing	0.968	D	0.725	prob.delet.	None	None	None	None	I
N/Y	0.9881	likely_pathogenic	0.9836	pathogenic	-0.174	Destabilizing	0.667	D	0.706	prob.neutral	D	0.542005513	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.