TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19810	59653;59654;59655	chr2:178592577;178592576;178592575	chr2:179457304;179457303;179457302
N2AB	18169	54730;54731;54732	chr2:178592577;178592576;178592575	chr2:179457304;179457303;179457302
N2A	17242	51949;51950;51951	chr2:178592577;178592576;178592575	chr2:179457304;179457303;179457302
N2B	10745	32458;32459;32460	chr2:178592577;178592576;178592575	chr2:179457304;179457303;179457302
Novex-1	10870	32833;32834;32835	chr2:178592577;178592576;178592575	chr2:179457304;179457303;179457302
Novex-2	10937	33034;33035;33036	chr2:178592577;178592576;178592575	chr2:179457304;179457303;179457302
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-119
• Domain position: 21
• Structural Position: 35
• Q(SASA): 0.0795
• 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	None	None	0.998	D	0.816	0.658	0.865813452579	gnomAD-4.0.0	1.59192E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85948E-06	0	0
I/V	None	None	0.333	N	0.188	0.173	0.485493271093	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.9634	likely_pathogenic	0.9596	pathogenic	-1.762	Destabilizing	0.992	D	0.681	prob.neutral	None	None	None	None	N
I/C	0.95	likely_pathogenic	0.9386	pathogenic	-1.088	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
I/D	0.9991	likely_pathogenic	0.9992	pathogenic	-1.104	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
I/E	0.9965	likely_pathogenic	0.9966	pathogenic	-0.944	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
I/F	0.6285	likely_pathogenic	0.5439	ambiguous	-0.91	Destabilizing	0.998	D	0.762	deleterious	N	0.518132951	None	None	N
I/G	0.9932	likely_pathogenic	0.9929	pathogenic	-2.228	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
I/H	0.9917	likely_pathogenic	0.9908	pathogenic	-1.412	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
I/K	0.9869	likely_pathogenic	0.9869	pathogenic	-1.169	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
I/L	0.325	likely_benign	0.2812	benign	-0.478	Destabilizing	0.889	D	0.399	neutral	N	0.513495135	None	None	N
I/M	0.4335	ambiguous	0.3741	ambiguous	-0.466	Destabilizing	0.998	D	0.724	prob.delet.	N	0.50233637	None	None	N
I/N	0.9867	likely_pathogenic	0.9865	pathogenic	-1.333	Destabilizing	0.999	D	0.84	deleterious	N	0.517820505	None	None	N
I/P	0.987	likely_pathogenic	0.9888	pathogenic	-0.88	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
I/Q	0.988	likely_pathogenic	0.9878	pathogenic	-1.244	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
I/R	0.9785	likely_pathogenic	0.9781	pathogenic	-0.885	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
I/S	0.9747	likely_pathogenic	0.9744	pathogenic	-2.09	Highly Destabilizing	0.998	D	0.816	deleterious	D	0.525482998	None	None	N
I/T	0.9493	likely_pathogenic	0.9425	pathogenic	-1.782	Destabilizing	0.989	D	0.767	deleterious	D	0.527405795	None	None	N
I/V	0.1878	likely_benign	0.1648	benign	-0.88	Destabilizing	0.333	N	0.188	neutral	N	0.427865158	None	None	N
I/W	0.9803	likely_pathogenic	0.9778	pathogenic	-1.126	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
I/Y	0.9605	likely_pathogenic	0.9505	pathogenic	-0.821	Destabilizing	1.0	D	0.787	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.