TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5616	17071;17072;17073	chr2:178732123;178732122;178732121	chr2:179596850;179596849;179596848
N2AB	5299	16120;16121;16122	chr2:178732123;178732122;178732121	chr2:179596850;179596849;179596848
N2A	4372	13339;13340;13341	chr2:178732123;178732122;178732121	chr2:179596850;179596849;179596848
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: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-39
• Domain position: 74
• Structural Position: 156
• Q(SASA): 0.0695
• Site annotation: disulfide
• 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/R	None	None	1.0	D	0.897	0.673	0.873153760803	gnomAD-4.0.0	1.20032E-06	None	None	disulfide	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
C/Y	rs1170057251	None	1.0	D	0.899	0.563	0.842083799564	gnomAD-3.1.2	6.57E-06	None	None	disulfide	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
C/Y	rs1170057251	None	1.0	D	0.899	0.563	0.842083799564	gnomAD-4.0.0	2.02985E-06	None	None	disulfide	None	N	None	1.74709E-05	0	None	0	0	None	0	0	0	0	3.40229E-05

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	0.7736	likely_pathogenic	0.804	pathogenic	-1.395	Destabilizing	0.998	D	0.736	prob.delet.	None	None	disulfide	None	N
C/D	0.9991	likely_pathogenic	0.9992	pathogenic	-1.642	Destabilizing	1.0	D	0.877	deleterious	None	None	disulfide	None	N
C/E	0.9991	likely_pathogenic	0.9993	pathogenic	-1.392	Destabilizing	1.0	D	0.891	deleterious	None	None	disulfide	None	N
C/F	0.7721	likely_pathogenic	0.7848	pathogenic	-0.772	Destabilizing	1.0	D	0.887	deleterious	D	0.555281738	disulfide	None	N
C/G	0.7204	likely_pathogenic	0.7651	pathogenic	-1.736	Destabilizing	1.0	D	0.864	deleterious	D	0.568158981	disulfide	None	N
C/H	0.9963	likely_pathogenic	0.9968	pathogenic	-1.935	Destabilizing	1.0	D	0.891	deleterious	None	None	disulfide	None	N
C/I	0.7828	likely_pathogenic	0.8072	pathogenic	-0.456	Destabilizing	1.0	D	0.81	deleterious	None	None	disulfide	None	N
C/K	0.9992	likely_pathogenic	0.9993	pathogenic	-0.994	Destabilizing	1.0	D	0.876	deleterious	None	None	disulfide	None	N
C/L	0.6424	likely_pathogenic	0.6908	pathogenic	-0.456	Destabilizing	0.999	D	0.771	deleterious	None	None	disulfide	None	N
C/M	0.8742	likely_pathogenic	0.9022	pathogenic	0.026	Stabilizing	1.0	D	0.833	deleterious	None	None	disulfide	None	N
C/N	0.995	likely_pathogenic	0.996	pathogenic	-1.696	Destabilizing	1.0	D	0.891	deleterious	None	None	disulfide	None	N
C/P	0.9987	likely_pathogenic	0.9988	pathogenic	-0.749	Destabilizing	1.0	D	0.891	deleterious	None	None	disulfide	None	N
C/Q	0.9969	likely_pathogenic	0.9976	pathogenic	-1.158	Destabilizing	1.0	D	0.905	deleterious	None	None	disulfide	None	N
C/R	0.9911	likely_pathogenic	0.9919	pathogenic	-1.52	Destabilizing	1.0	D	0.897	deleterious	D	0.568158981	disulfide	None	N
C/S	0.938	likely_pathogenic	0.9531	pathogenic	-1.926	Destabilizing	1.0	D	0.797	deleterious	D	0.568158981	disulfide	None	N
C/T	0.9471	likely_pathogenic	0.9563	pathogenic	-1.51	Destabilizing	1.0	D	0.808	deleterious	None	None	disulfide	None	N
C/V	0.6358	likely_pathogenic	0.6564	pathogenic	-0.749	Destabilizing	0.999	D	0.785	deleterious	None	None	disulfide	None	N
C/W	0.9807	likely_pathogenic	0.982	pathogenic	-1.266	Destabilizing	1.0	D	0.866	deleterious	D	0.568158981	disulfide	None	N
C/Y	0.9557	likely_pathogenic	0.9559	pathogenic	-1.026	Destabilizing	1.0	D	0.899	deleterious	D	0.568158981	disulfide	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.