TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16331	49216;49217;49218	chr2:178614523;178614522;178614521	chr2:179479250;179479249;179479248
N2AB	14690	44293;44294;44295	chr2:178614523;178614522;178614521	chr2:179479250;179479249;179479248
N2A	13763	41512;41513;41514	chr2:178614523;178614522;178614521	chr2:179479250;179479249;179479248
N2B	7266	22021;22022;22023	chr2:178614523;178614522;178614521	chr2:179479250;179479249;179479248
Novex-1	7391	22396;22397;22398	chr2:178614523;178614522;178614521	chr2:179479250;179479249;179479248
Novex-2	7458	22597;22598;22599	chr2:178614523;178614522;178614521	chr2:179479250;179479249;179479248
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-110
• Domain position: 70
• Structural Position: 156
• Q(SASA): 0.0945
• 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/T	None	None	0.939	D	0.735	0.426	0.629781192331	gnomAD-4.0.0	2.73913E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59963E-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	0.9249	likely_pathogenic	0.9156	pathogenic	-2.024	Highly Destabilizing	0.91	D	0.701	prob.neutral	None	None	None	None	N
I/C	0.9787	likely_pathogenic	0.9793	pathogenic	-1.302	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
I/D	0.9999	likely_pathogenic	0.9998	pathogenic	-1.864	Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
I/E	0.999	likely_pathogenic	0.999	pathogenic	-1.707	Destabilizing	0.993	D	0.835	deleterious	None	None	None	None	N
I/F	0.9218	likely_pathogenic	0.9305	pathogenic	-1.237	Destabilizing	0.991	D	0.733	prob.delet.	D	0.561863686	None	None	N
I/G	0.9967	likely_pathogenic	0.9964	pathogenic	-2.513	Highly Destabilizing	0.993	D	0.835	deleterious	None	None	None	None	N
I/H	0.9995	likely_pathogenic	0.9995	pathogenic	-1.941	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
I/K	0.9977	likely_pathogenic	0.9977	pathogenic	-1.318	Destabilizing	0.993	D	0.837	deleterious	None	None	None	None	N
I/L	0.2954	likely_benign	0.3082	benign	-0.662	Destabilizing	0.58	D	0.454	neutral	N	0.446206612	None	None	N
I/M	0.4403	ambiguous	0.4671	ambiguous	-0.582	Destabilizing	0.991	D	0.695	prob.neutral	N	0.500651228	None	None	N
I/N	0.9977	likely_pathogenic	0.9977	pathogenic	-1.457	Destabilizing	0.997	D	0.834	deleterious	D	0.606363779	None	None	N
I/P	0.9986	likely_pathogenic	0.9985	pathogenic	-1.091	Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	N
I/Q	0.9979	likely_pathogenic	0.9979	pathogenic	-1.415	Destabilizing	0.998	D	0.842	deleterious	None	None	None	None	N
I/R	0.9964	likely_pathogenic	0.9963	pathogenic	-1.017	Destabilizing	0.998	D	0.842	deleterious	None	None	None	None	N
I/S	0.9903	likely_pathogenic	0.9897	pathogenic	-2.176	Highly Destabilizing	0.991	D	0.806	deleterious	D	0.605433628	None	None	N
I/T	0.9317	likely_pathogenic	0.9263	pathogenic	-1.876	Destabilizing	0.939	D	0.735	prob.delet.	D	0.603908937	None	None	N
I/V	0.1388	likely_benign	0.1459	benign	-1.091	Destabilizing	0.02	N	0.285	neutral	N	0.437083429	None	None	N
I/W	0.9992	likely_pathogenic	0.9994	pathogenic	-1.543	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
I/Y	0.9971	likely_pathogenic	0.9974	pathogenic	-1.217	Destabilizing	0.998	D	0.734	prob.delet.	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.