TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21577	64954;64955;64956	chr2:178584912;178584911;178584910	chr2:179449639;179449638;179449637
N2AB	19936	60031;60032;60033	chr2:178584912;178584911;178584910	chr2:179449639;179449638;179449637
N2A	19009	57250;57251;57252	chr2:178584912;178584911;178584910	chr2:179449639;179449638;179449637
N2B	12512	37759;37760;37761	chr2:178584912;178584911;178584910	chr2:179449639;179449638;179449637
Novex-1	12637	38134;38135;38136	chr2:178584912;178584911;178584910	chr2:179449639;179449638;179449637
Novex-2	12704	38335;38336;38337	chr2:178584912;178584911;178584910	chr2:179449639;179449638;179449637
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-44
• Domain position: 19
• Structural Position: 20
• Q(SASA): 0.13
• 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
C/W	None	None	0.997	N	0.782	0.388	0.701073398044	gnomAD-4.0.0	6.84407E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99637E-07	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
C/A	0.6137	likely_pathogenic	0.629	pathogenic	-1.483	Destabilizing	0.559	D	0.531	neutral	None	None	None	None	N
C/D	0.999	likely_pathogenic	0.9992	pathogenic	-1.463	Destabilizing	0.956	D	0.818	deleterious	None	None	None	None	N
C/E	0.9992	likely_pathogenic	0.9993	pathogenic	-1.244	Destabilizing	0.956	D	0.825	deleterious	None	None	None	None	N
C/F	0.7905	likely_pathogenic	0.8124	pathogenic	-1.219	Destabilizing	0.97	D	0.782	deleterious	N	0.500428972	None	None	N
C/G	0.6874	likely_pathogenic	0.7087	pathogenic	-1.822	Destabilizing	0.698	D	0.741	deleterious	N	0.487125501	None	None	N
C/H	0.9956	likely_pathogenic	0.9964	pathogenic	-2.236	Highly Destabilizing	0.998	D	0.813	deleterious	None	None	None	None	N
C/I	0.6387	likely_pathogenic	0.655	pathogenic	-0.586	Destabilizing	0.978	D	0.793	deleterious	None	None	None	None	N
C/K	0.9993	likely_pathogenic	0.9994	pathogenic	-0.775	Destabilizing	0.956	D	0.811	deleterious	None	None	None	None	N
C/L	0.6962	likely_pathogenic	0.7214	pathogenic	-0.586	Destabilizing	0.86	D	0.695	prob.neutral	None	None	None	None	N
C/M	0.846	likely_pathogenic	0.8693	pathogenic	-0.126	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
C/N	0.9932	likely_pathogenic	0.9946	pathogenic	-1.395	Destabilizing	0.956	D	0.827	deleterious	None	None	None	None	N
C/P	0.9985	likely_pathogenic	0.9988	pathogenic	-0.861	Destabilizing	0.978	D	0.823	deleterious	None	None	None	None	N
C/Q	0.9959	likely_pathogenic	0.9968	pathogenic	-1.008	Destabilizing	0.956	D	0.825	deleterious	None	None	None	None	N
C/R	0.9932	likely_pathogenic	0.9947	pathogenic	-1.222	Destabilizing	0.942	D	0.82	deleterious	N	0.49864639	None	None	N
C/S	0.8309	likely_pathogenic	0.8493	pathogenic	-1.655	Destabilizing	0.058	N	0.452	neutral	N	0.468767756	None	None	N
C/T	0.8652	likely_pathogenic	0.8758	pathogenic	-1.239	Destabilizing	0.754	D	0.721	prob.delet.	None	None	None	None	N
C/V	0.456	ambiguous	0.4657	ambiguous	-0.861	Destabilizing	0.86	D	0.741	deleterious	None	None	None	None	N
C/W	0.9889	likely_pathogenic	0.9901	pathogenic	-1.585	Destabilizing	0.997	D	0.782	deleterious	N	0.475769195	None	None	N
C/Y	0.9602	likely_pathogenic	0.9658	pathogenic	-1.306	Destabilizing	0.99	D	0.797	deleterious	N	0.480288646	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.