TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34426	103501;103502;103503	chr2:178533339;178533338;178533337	chr2:179398066;179398065;179398064
N2AB	32785	98578;98579;98580	chr2:178533339;178533338;178533337	chr2:179398066;179398065;179398064
N2A	31858	95797;95798;95799	chr2:178533339;178533338;178533337	chr2:179398066;179398065;179398064
N2B	25361	76306;76307;76308	chr2:178533339;178533338;178533337	chr2:179398066;179398065;179398064
Novex-1	25486	76681;76682;76683	chr2:178533339;178533338;178533337	chr2:179398066;179398065;179398064
Novex-2	25553	76882;76883;76884	chr2:178533339;178533338;178533337	chr2:179398066;179398065;179398064
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: Ig-162
• Domain position: 64
• Structural Position: 144
• Q(SASA): 0.0902
• 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	rs375049689	-0.079	1.0	N	0.797	0.418	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
T/P	None	None	1.0	N	0.8	0.562	0.42828666871	gnomAD-4.0.0	1.59151E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85763E-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	0.3771	ambiguous	0.3358	benign	-0.753	Destabilizing	0.999	D	0.549	neutral	N	0.426001076	None	None	N
T/C	0.6938	likely_pathogenic	0.6659	pathogenic	-1.278	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
T/D	0.9939	likely_pathogenic	0.9928	pathogenic	-2.705	Highly Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
T/E	0.9928	likely_pathogenic	0.9917	pathogenic	-2.544	Highly Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
T/F	0.9852	likely_pathogenic	0.9868	pathogenic	-0.744	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
T/G	0.9079	likely_pathogenic	0.8939	pathogenic	-1.06	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
T/H	0.9819	likely_pathogenic	0.9823	pathogenic	-1.342	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
T/I	0.8188	likely_pathogenic	0.8173	pathogenic	0.011	Stabilizing	1.0	D	0.797	deleterious	N	0.483163868	None	None	N
T/K	0.9843	likely_pathogenic	0.9838	pathogenic	-0.77	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
T/L	0.6237	likely_pathogenic	0.632	pathogenic	0.011	Stabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
T/M	0.5879	likely_pathogenic	0.5859	pathogenic	-0.153	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
T/N	0.9115	likely_pathogenic	0.8959	pathogenic	-1.66	Destabilizing	1.0	D	0.773	deleterious	N	0.513938802	None	None	N
T/P	0.7059	likely_pathogenic	0.7423	pathogenic	-0.214	Destabilizing	1.0	D	0.8	deleterious	N	0.51666594	None	None	N
T/Q	0.9788	likely_pathogenic	0.9772	pathogenic	-1.541	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
T/R	0.9702	likely_pathogenic	0.9713	pathogenic	-0.838	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
T/S	0.621	likely_pathogenic	0.5524	ambiguous	-1.531	Destabilizing	0.999	D	0.59	neutral	N	0.497386746	None	None	N
T/V	0.5288	ambiguous	0.5331	ambiguous	-0.214	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
T/W	0.9985	likely_pathogenic	0.9986	pathogenic	-1.122	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
T/Y	0.9928	likely_pathogenic	0.994	pathogenic	-0.622	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.