TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5955	18088;18089;18090	chr2:178730670;178730669;178730668	chr2:179595397;179595396;179595395
N2AB	5638	17137;17138;17139	chr2:178730670;178730669;178730668	chr2:179595397;179595396;179595395
N2A	4711	14356;14357;14358	chr2:178730670;178730669;178730668	chr2:179595397;179595396;179595395
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-43
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.4699
• 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
D/G	None	None	0.978	N	0.533	0.372	0.200317383148	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
D/A	0.4148	ambiguous	0.4132	ambiguous	-0.59	Destabilizing	0.978	D	0.544	neutral	N	0.493135754	None	None	N
D/C	0.8611	likely_pathogenic	0.8587	pathogenic	-0.14	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
D/E	0.2853	likely_benign	0.2896	benign	-0.564	Destabilizing	0.37	N	0.263	neutral	N	0.493249496	None	None	N
D/F	0.8838	likely_pathogenic	0.8941	pathogenic	-0.417	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
D/G	0.168	likely_benign	0.1636	benign	-0.859	Destabilizing	0.978	D	0.533	neutral	N	0.509909673	None	None	N
D/H	0.6375	likely_pathogenic	0.6272	pathogenic	-0.584	Destabilizing	0.999	D	0.598	neutral	D	0.529686659	None	None	N
D/I	0.8785	likely_pathogenic	0.8908	pathogenic	0.096	Stabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
D/K	0.7237	likely_pathogenic	0.7257	pathogenic	-0.229	Destabilizing	0.983	D	0.554	neutral	None	None	None	None	N
D/L	0.7981	likely_pathogenic	0.7949	pathogenic	0.096	Stabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
D/M	0.8881	likely_pathogenic	0.8878	pathogenic	0.474	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
D/N	0.1159	likely_benign	0.1124	benign	-0.523	Destabilizing	0.576	D	0.256	neutral	N	0.461075576	None	None	N
D/P	0.9904	likely_pathogenic	0.9901	pathogenic	-0.109	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	N
D/Q	0.6419	likely_pathogenic	0.6358	pathogenic	-0.449	Destabilizing	0.995	D	0.573	neutral	None	None	None	None	N
D/R	0.7543	likely_pathogenic	0.7477	pathogenic	-0.059	Destabilizing	0.995	D	0.624	neutral	None	None	None	None	N
D/S	0.2844	likely_benign	0.2794	benign	-0.694	Destabilizing	0.983	D	0.473	neutral	None	None	None	None	N
D/T	0.7202	likely_pathogenic	0.726	pathogenic	-0.485	Destabilizing	0.995	D	0.547	neutral	None	None	None	None	N
D/V	0.7013	likely_pathogenic	0.7196	pathogenic	-0.109	Destabilizing	0.997	D	0.684	prob.neutral	N	0.498010826	None	None	N
D/W	0.9694	likely_pathogenic	0.97	pathogenic	-0.25	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
D/Y	0.5142	ambiguous	0.5303	ambiguous	-0.194	Destabilizing	1.0	D	0.686	prob.neutral	N	0.511835893	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.