TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29545	88858;88859;88860	chr2:178554714;178554713;178554712	chr2:179419441;179419440;179419439
N2AB	27904	83935;83936;83937	chr2:178554714;178554713;178554712	chr2:179419441;179419440;179419439
N2A	26977	81154;81155;81156	chr2:178554714;178554713;178554712	chr2:179419441;179419440;179419439
N2B	20480	61663;61664;61665	chr2:178554714;178554713;178554712	chr2:179419441;179419440;179419439
Novex-1	20605	62038;62039;62040	chr2:178554714;178554713;178554712	chr2:179419441;179419440;179419439
Novex-2	20672	62239;62240;62241	chr2:178554714;178554713;178554712	chr2:179419441;179419440;179419439
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-103
• Domain position: 13
• Structural Position: 14
• Q(SASA): 0.4713
• 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
T/I	rs1302609593	0.15	0.988	N	0.424	0.297	0.3349148499	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
T/I	rs1302609593	0.15	0.988	N	0.424	0.297	0.3349148499	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1302609593	0.15	0.988	N	0.424	0.297	0.3349148499	gnomAD-4.0.0	2.56187E-06	None	None	None	None	N	None	0	0	None	0	2.42377E-05	None	0	0	2.39263E-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
T/A	0.101	likely_benign	0.0985	benign	-0.62	Destabilizing	0.704	D	0.368	neutral	N	0.4303211	None	None	N
T/C	0.5277	ambiguous	0.535	ambiguous	-0.363	Destabilizing	0.999	D	0.448	neutral	None	None	None	None	N
T/D	0.4958	ambiguous	0.4346	ambiguous	0.05	Stabilizing	0.939	D	0.405	neutral	None	None	None	None	N
T/E	0.4306	ambiguous	0.3821	ambiguous	0.022	Stabilizing	0.939	D	0.375	neutral	None	None	None	None	N
T/F	0.3792	ambiguous	0.3708	ambiguous	-0.802	Destabilizing	0.997	D	0.476	neutral	None	None	None	None	N
T/G	0.2857	likely_benign	0.2741	benign	-0.842	Destabilizing	0.939	D	0.429	neutral	None	None	None	None	N
T/H	0.3082	likely_benign	0.2937	benign	-1.148	Destabilizing	0.999	D	0.453	neutral	None	None	None	None	N
T/I	0.3188	likely_benign	0.3161	benign	-0.134	Destabilizing	0.988	D	0.424	neutral	N	0.489678834	None	None	N
T/K	0.3112	likely_benign	0.2907	benign	-0.583	Destabilizing	0.079	N	0.134	neutral	None	None	None	None	N
T/L	0.1453	likely_benign	0.1409	benign	-0.134	Destabilizing	0.969	D	0.378	neutral	None	None	None	None	N
T/M	0.0942	likely_benign	0.0978	benign	0.123	Stabilizing	0.999	D	0.427	neutral	None	None	None	None	N
T/N	0.1241	likely_benign	0.1147	benign	-0.432	Destabilizing	0.92	D	0.387	neutral	N	0.377449407	None	None	N
T/P	0.582	likely_pathogenic	0.5738	pathogenic	-0.264	Destabilizing	0.988	D	0.414	neutral	N	0.5180948	None	None	N
T/Q	0.2847	likely_benign	0.2714	benign	-0.63	Destabilizing	0.982	D	0.417	neutral	None	None	None	None	N
T/R	0.2892	likely_benign	0.2715	benign	-0.344	Destabilizing	0.884	D	0.403	neutral	None	None	None	None	N
T/S	0.1275	likely_benign	0.1256	benign	-0.711	Destabilizing	0.31	N	0.123	neutral	N	0.419373387	None	None	N
T/V	0.2163	likely_benign	0.2147	benign	-0.264	Destabilizing	0.969	D	0.343	neutral	None	None	None	None	N
T/W	0.7157	likely_pathogenic	0.7078	pathogenic	-0.742	Destabilizing	0.999	D	0.547	neutral	None	None	None	None	N
T/Y	0.3586	ambiguous	0.3319	benign	-0.502	Destabilizing	0.997	D	0.475	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.