TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9518	28777;28778;28779	chr2:178709767;178709766;178709765	chr2:179574494;179574493;179574492
N2AB	9201	27826;27827;27828	chr2:178709767;178709766;178709765	chr2:179574494;179574493;179574492
N2A	8274	25045;25046;25047	chr2:178709767;178709766;178709765	chr2:179574494;179574493;179574492
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-81
• Domain position: 26
• Structural Position: 38
• Q(SASA): 0.3606
• 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
A/S	None	None	0.046	None	0.147	0.108	0.231231049324	gnomAD-4.0.0	1.59125E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85798E-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
A/C	0.6964	likely_pathogenic	0.7238	pathogenic	-0.732	Destabilizing	0.999	D	0.513	neutral	None	None	None	None	N
A/D	0.6437	likely_pathogenic	0.7374	pathogenic	-0.298	Destabilizing	0.896	D	0.573	neutral	None	None	None	None	N
A/E	0.5269	ambiguous	0.6247	pathogenic	-0.436	Destabilizing	0.919	D	0.531	neutral	None	None	None	None	N
A/F	0.4734	ambiguous	0.5133	ambiguous	-0.82	Destabilizing	0.996	D	0.621	neutral	None	None	None	None	N
A/G	0.2309	likely_benign	0.2569	benign	-0.352	Destabilizing	0.64	D	0.469	neutral	None	None	None	None	N
A/H	0.7109	likely_pathogenic	0.7646	pathogenic	-0.43	Destabilizing	0.999	D	0.622	neutral	None	None	None	None	N
A/I	0.4316	ambiguous	0.443	ambiguous	-0.228	Destabilizing	0.976	D	0.519	neutral	None	None	None	None	N
A/K	0.7768	likely_pathogenic	0.8376	pathogenic	-0.597	Destabilizing	0.919	D	0.521	neutral	None	None	None	None	N
A/L	0.3016	likely_benign	0.3251	benign	-0.228	Destabilizing	0.919	D	0.513	neutral	None	None	None	None	N
A/M	0.3602	ambiguous	0.3681	ambiguous	-0.286	Destabilizing	0.999	D	0.561	neutral	None	None	None	None	N
A/N	0.4596	ambiguous	0.491	ambiguous	-0.257	Destabilizing	0.976	D	0.568	neutral	None	None	None	None	N
A/P	0.951	likely_pathogenic	0.9559	pathogenic	-0.204	Destabilizing	0.984	D	0.519	neutral	None	None	None	None	N
A/Q	0.5445	ambiguous	0.6086	pathogenic	-0.51	Destabilizing	0.988	D	0.565	neutral	None	None	None	None	N
A/R	0.6788	likely_pathogenic	0.7574	pathogenic	-0.187	Destabilizing	0.976	D	0.559	neutral	None	None	None	None	N
A/S	0.0954	likely_benign	0.1064	benign	-0.512	Destabilizing	0.046	N	0.147	neutral	None	None	None	None	N
A/T	0.1243	likely_benign	0.1192	benign	-0.561	Destabilizing	0.046	N	0.141	neutral	None	None	None	None	N
A/V	0.219	likely_benign	0.2315	benign	-0.204	Destabilizing	0.896	D	0.471	neutral	None	None	None	None	N
A/W	0.8909	likely_pathogenic	0.9148	pathogenic	-0.988	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
A/Y	0.6992	likely_pathogenic	0.7382	pathogenic	-0.613	Destabilizing	0.996	D	0.626	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.