TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4882	14869;14870;14871	chr2:178735802;178735801;178735800	chr2:179600529;179600528;179600527
N2AB	4565	13918;13919;13920	chr2:178735802;178735801;178735800	chr2:179600529;179600528;179600527
N2A	3638	11137;11138;11139	chr2:178735802;178735801;178735800	chr2:179600529;179600528;179600527
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: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-31
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.0761
• 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
L/F	rs1197344089	None	0.993	D	0.839	0.379	0.639464360942	gnomAD-4.0.0	1.36852E-06	None	None	None	None	N	None	0	2.23674E-05	None	0	0	None	0	0	8.99465E-07	0	0
L/S	None	None	0.997	D	0.911	0.621	0.867739572965	gnomAD-4.0.0	2.73704E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59789E-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
L/A	0.8351	likely_pathogenic	0.8118	pathogenic	-2.749	Highly Destabilizing	0.983	D	0.765	deleterious	None	None	None	None	N
L/C	0.8342	likely_pathogenic	0.8196	pathogenic	-1.864	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/D	0.9952	likely_pathogenic	0.9954	pathogenic	-3.167	Highly Destabilizing	0.999	D	0.925	deleterious	None	None	None	None	N
L/E	0.9726	likely_pathogenic	0.9728	pathogenic	-2.839	Highly Destabilizing	0.998	D	0.915	deleterious	None	None	None	None	N
L/F	0.566	likely_pathogenic	0.4888	ambiguous	-1.635	Destabilizing	0.993	D	0.839	deleterious	D	0.631424537	None	None	N
L/G	0.9428	likely_pathogenic	0.941	pathogenic	-3.382	Highly Destabilizing	0.998	D	0.917	deleterious	None	None	None	None	N
L/H	0.9527	likely_pathogenic	0.9523	pathogenic	-2.982	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
L/I	0.183	likely_benign	0.1612	benign	-0.854	Destabilizing	0.966	D	0.625	neutral	None	None	None	None	N
L/K	0.9612	likely_pathogenic	0.966	pathogenic	-1.996	Destabilizing	0.995	D	0.92	deleterious	None	None	None	None	N
L/M	0.1888	likely_benign	0.172	benign	-0.954	Destabilizing	0.898	D	0.568	neutral	D	0.665823624	None	None	N
L/N	0.9669	likely_pathogenic	0.9662	pathogenic	-2.665	Highly Destabilizing	0.999	D	0.925	deleterious	None	None	None	None	N
L/P	0.9848	likely_pathogenic	0.9867	pathogenic	-1.475	Destabilizing	0.999	D	0.924	deleterious	None	None	None	None	N
L/Q	0.9138	likely_pathogenic	0.9158	pathogenic	-2.317	Highly Destabilizing	0.998	D	0.928	deleterious	None	None	None	None	N
L/R	0.9315	likely_pathogenic	0.9378	pathogenic	-2.039	Highly Destabilizing	0.998	D	0.916	deleterious	None	None	None	None	N
L/S	0.9608	likely_pathogenic	0.9592	pathogenic	-3.317	Highly Destabilizing	0.997	D	0.911	deleterious	D	0.763804758	None	None	N
L/T	0.881	likely_pathogenic	0.8695	pathogenic	-2.815	Highly Destabilizing	0.995	D	0.847	deleterious	None	None	None	None	N
L/V	0.1993	likely_benign	0.173	benign	-1.475	Destabilizing	0.955	D	0.642	neutral	N	0.520227068	None	None	N
L/W	0.8643	likely_pathogenic	0.8686	pathogenic	-2.016	Highly Destabilizing	1.0	D	0.907	deleterious	D	0.763804758	None	None	N
L/Y	0.894	likely_pathogenic	0.8757	pathogenic	-1.771	Destabilizing	0.998	D	0.883	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.