TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18491	55696;55697;55698	chr2:178601526;178601525;178601524	chr2:179466253;179466252;179466251
N2AB	16850	50773;50774;50775	chr2:178601526;178601525;178601524	chr2:179466253;179466252;179466251
N2A	15923	47992;47993;47994	chr2:178601526;178601525;178601524	chr2:179466253;179466252;179466251
N2B	9426	28501;28502;28503	chr2:178601526;178601525;178601524	chr2:179466253;179466252;179466251
Novex-1	9551	28876;28877;28878	chr2:178601526;178601525;178601524	chr2:179466253;179466252;179466251
Novex-2	9618	29077;29078;29079	chr2:178601526;178601525;178601524	chr2:179466253;179466252;179466251
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: Fn3-22
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.4789
• 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	0.896	N	0.405	0.374	0.648347046735	gnomAD-4.0.0	3.18764E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.7259E-06	0	0
I/V	None	None	0.004	N	0.087	0.076	0.485493271093	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.8011	likely_pathogenic	0.8464	pathogenic	-1.265	Destabilizing	0.702	D	0.414	neutral	None	None	None	None	N
I/C	0.8373	likely_pathogenic	0.8798	pathogenic	-1.131	Destabilizing	0.999	D	0.497	neutral	None	None	None	None	N
I/D	0.9842	likely_pathogenic	0.9874	pathogenic	-1.563	Destabilizing	0.996	D	0.595	neutral	None	None	None	None	N
I/E	0.9571	likely_pathogenic	0.9645	pathogenic	-1.615	Destabilizing	0.988	D	0.565	neutral	None	None	None	None	N
I/F	0.6548	likely_pathogenic	0.6476	pathogenic	-1.418	Destabilizing	0.984	D	0.453	neutral	N	0.476425348	None	None	N
I/G	0.9622	likely_pathogenic	0.9707	pathogenic	-1.478	Destabilizing	0.988	D	0.509	neutral	None	None	None	None	N
I/H	0.952	likely_pathogenic	0.9605	pathogenic	-0.934	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
I/K	0.8857	likely_pathogenic	0.9129	pathogenic	-0.773	Destabilizing	0.988	D	0.572	neutral	None	None	None	None	N
I/L	0.3786	ambiguous	0.3979	ambiguous	-0.776	Destabilizing	0.437	N	0.188	neutral	N	0.496471521	None	None	N
I/M	0.2976	likely_benign	0.3365	benign	-0.576	Destabilizing	0.984	D	0.509	neutral	N	0.477639889	None	None	N
I/N	0.8322	likely_pathogenic	0.8703	pathogenic	-0.697	Destabilizing	0.995	D	0.587	neutral	N	0.488235726	None	None	N
I/P	0.9359	likely_pathogenic	0.9449	pathogenic	-0.91	Destabilizing	0.996	D	0.593	neutral	None	None	None	None	N
I/Q	0.9217	likely_pathogenic	0.94	pathogenic	-1.018	Destabilizing	0.996	D	0.599	neutral	None	None	None	None	N
I/R	0.871	likely_pathogenic	0.8925	pathogenic	-0.24	Destabilizing	0.996	D	0.593	neutral	None	None	None	None	N
I/S	0.8215	likely_pathogenic	0.8628	pathogenic	-1.138	Destabilizing	0.984	D	0.46	neutral	N	0.469068288	None	None	N
I/T	0.536	ambiguous	0.6457	pathogenic	-1.09	Destabilizing	0.896	D	0.405	neutral	N	0.498973108	None	None	N
I/V	0.0731	likely_benign	0.0789	benign	-0.91	Destabilizing	0.004	N	0.087	neutral	N	0.3966326	None	None	N
I/W	0.9816	likely_pathogenic	0.9855	pathogenic	-1.484	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
I/Y	0.9229	likely_pathogenic	0.932	pathogenic	-1.14	Destabilizing	0.996	D	0.521	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.