TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26406	79441;79442;79443	chr2:178566916;178566915;178566914	chr2:179431643;179431642;179431641
N2AB	24765	74518;74519;74520	chr2:178566916;178566915;178566914	chr2:179431643;179431642;179431641
N2A	23838	71737;71738;71739	chr2:178566916;178566915;178566914	chr2:179431643;179431642;179431641
N2B	17341	52246;52247;52248	chr2:178566916;178566915;178566914	chr2:179431643;179431642;179431641
Novex-1	17466	52621;52622;52623	chr2:178566916;178566915;178566914	chr2:179431643;179431642;179431641
Novex-2	17533	52822;52823;52824	chr2:178566916;178566915;178566914	chr2:179431643;179431642;179431641
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-80
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.1457
• 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/Y	rs727505223	None	0.97	N	0.746	0.349	0.789754116976	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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	0.4448	ambiguous	0.5264	ambiguous	-1.549	Destabilizing	0.559	D	0.541	neutral	None	None	None	None	N
C/D	0.9218	likely_pathogenic	0.9487	pathogenic	-1.054	Destabilizing	0.993	D	0.798	deleterious	None	None	None	None	N
C/E	0.9246	likely_pathogenic	0.9458	pathogenic	-0.886	Destabilizing	0.978	D	0.804	deleterious	None	None	None	None	N
C/F	0.3686	ambiguous	0.4667	ambiguous	-0.984	Destabilizing	0.942	D	0.727	prob.delet.	N	0.518268158	None	None	N
C/G	0.2905	likely_benign	0.3677	ambiguous	-1.882	Destabilizing	0.97	D	0.744	deleterious	N	0.467031261	None	None	N
C/H	0.7178	likely_pathogenic	0.8199	pathogenic	-2.196	Highly Destabilizing	0.998	D	0.802	deleterious	None	None	None	None	N
C/I	0.5296	ambiguous	0.577	pathogenic	-0.678	Destabilizing	0.754	D	0.593	neutral	None	None	None	None	N
C/K	0.931	likely_pathogenic	0.9599	pathogenic	-1.085	Destabilizing	0.978	D	0.786	deleterious	None	None	None	None	N
C/L	0.522	ambiguous	0.6042	pathogenic	-0.678	Destabilizing	0.559	D	0.595	neutral	None	None	None	None	N
C/M	0.5936	likely_pathogenic	0.647	pathogenic	0.104	Stabilizing	0.978	D	0.692	prob.neutral	None	None	None	None	N
C/N	0.6262	likely_pathogenic	0.6878	pathogenic	-1.358	Destabilizing	0.993	D	0.819	deleterious	None	None	None	None	N
C/P	0.9932	likely_pathogenic	0.995	pathogenic	-0.943	Destabilizing	0.993	D	0.806	deleterious	None	None	None	None	N
C/Q	0.7472	likely_pathogenic	0.8214	pathogenic	-1.085	Destabilizing	0.993	D	0.815	deleterious	None	None	None	None	N
C/R	0.7232	likely_pathogenic	0.8161	pathogenic	-1.272	Destabilizing	0.97	D	0.821	deleterious	N	0.454600682	None	None	N
C/S	0.2813	likely_benign	0.3374	benign	-1.731	Destabilizing	0.904	D	0.662	neutral	N	0.366938838	None	None	N
C/T	0.358	ambiguous	0.4115	ambiguous	-1.383	Destabilizing	0.86	D	0.658	neutral	None	None	None	None	N
C/V	0.4193	ambiguous	0.4514	ambiguous	-0.943	Destabilizing	0.019	N	0.474	neutral	None	None	None	None	N
C/W	0.7738	likely_pathogenic	0.8541	pathogenic	-1.254	Destabilizing	0.997	D	0.735	prob.delet.	N	0.465657565	None	None	N
C/Y	0.5682	likely_pathogenic	0.6772	pathogenic	-1.09	Destabilizing	0.97	D	0.746	deleterious	N	0.472240931	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.