TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7211	21856;21857;21858	chr2:178723469;178723468;178723467	chr2:179588196;179588195;179588194
N2AB	6894	20905;20906;20907	chr2:178723469;178723468;178723467	chr2:179588196;179588195;179588194
N2A	5967	18124;18125;18126	chr2:178723469;178723468;178723467	chr2:179588196;179588195;179588194
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-56
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0825
• 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
V/I	None	None	0.37	D	0.242	0.26	0.546393912413	gnomAD-4.0.0	1.59255E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85997E-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
V/A	0.4253	ambiguous	0.4033	ambiguous	-2.243	Highly Destabilizing	0.978	D	0.615	neutral	N	0.440909026	None	None	N
V/C	0.9454	likely_pathogenic	0.9487	pathogenic	-1.899	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/D	0.9888	likely_pathogenic	0.9884	pathogenic	-2.903	Highly Destabilizing	0.999	D	0.839	deleterious	D	0.547587462	None	None	N
V/E	0.9739	likely_pathogenic	0.974	pathogenic	-2.695	Highly Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
V/F	0.6214	likely_pathogenic	0.6277	pathogenic	-1.304	Destabilizing	0.997	D	0.841	deleterious	D	0.529229717	None	None	N
V/G	0.7356	likely_pathogenic	0.7095	pathogenic	-2.771	Highly Destabilizing	0.999	D	0.829	deleterious	N	0.51540465	None	None	N
V/H	0.9901	likely_pathogenic	0.9908	pathogenic	-2.456	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/I	0.104	likely_benign	0.1046	benign	-0.77	Destabilizing	0.37	N	0.242	neutral	D	0.523693486	None	None	N
V/K	0.9855	likely_pathogenic	0.9864	pathogenic	-1.875	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
V/L	0.5027	ambiguous	0.483	ambiguous	-0.77	Destabilizing	0.9	D	0.537	neutral	N	0.516605964	None	None	N
V/M	0.5369	ambiguous	0.5352	ambiguous	-0.917	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
V/N	0.9725	likely_pathogenic	0.9709	pathogenic	-2.18	Highly Destabilizing	0.999	D	0.866	deleterious	None	None	None	None	N
V/P	0.9881	likely_pathogenic	0.9892	pathogenic	-1.235	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
V/Q	0.9729	likely_pathogenic	0.9733	pathogenic	-2.047	Highly Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
V/R	0.9676	likely_pathogenic	0.9686	pathogenic	-1.653	Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
V/S	0.8061	likely_pathogenic	0.7967	pathogenic	-2.794	Highly Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
V/T	0.7139	likely_pathogenic	0.6917	pathogenic	-2.449	Highly Destabilizing	0.992	D	0.698	prob.neutral	None	None	None	None	N
V/W	0.9926	likely_pathogenic	0.9939	pathogenic	-1.809	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/Y	0.963	likely_pathogenic	0.9641	pathogenic	-1.472	Destabilizing	0.999	D	0.825	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.