TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5174	15745;15746;15747	chr2:178733869;178733868;178733867	chr2:179598596;179598595;179598594
N2AB	4857	14794;14795;14796	chr2:178733869;178733868;178733867	chr2:179598596;179598595;179598594
N2A	3930	12013;12014;12015	chr2:178733869;178733868;178733867	chr2:179598596;179598595;179598594
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-35
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2417
• Predicted PPI site: I

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/G	None	None	0.901	N	0.777	0.28	0.656830896108	gnomAD-4.0.0	1.62443E-06	None	None	None	None	I	None	0	2.33372E-05	None	0	0	None	0	0	0	0	0
V/I	rs1169617547	-0.474	0.008	N	0.377	0.087	0.257786959452	gnomAD-2.1.1	4.11E-06	None	None	None	None	I	None	0	2.99E-05	None	0	0	None	0	None	0	0	0
V/I	rs1169617547	-0.474	0.008	N	0.377	0.087	0.257786959452	gnomAD-4.0.0	3.24997E-06	None	None	None	None	I	None	0	2.33492E-05	None	0	0	None	0	0	0	1.46007E-05	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	0.2329	likely_benign	0.314	benign	-1.668	Destabilizing	0.349	N	0.561	neutral	N	0.445633119	None	None	I
V/C	0.8836	likely_pathogenic	0.9294	pathogenic	-1.159	Destabilizing	0.996	D	0.731	prob.delet.	None	None	None	None	I
V/D	0.8893	likely_pathogenic	0.9388	pathogenic	-1.428	Destabilizing	0.858	D	0.777	deleterious	None	None	None	None	I
V/E	0.8545	likely_pathogenic	0.9093	pathogenic	-1.359	Destabilizing	0.018	N	0.525	neutral	N	0.449771049	None	None	I
V/F	0.4417	ambiguous	0.5475	ambiguous	-1.099	Destabilizing	0.923	D	0.791	deleterious	None	None	None	None	I
V/G	0.4601	ambiguous	0.5666	pathogenic	-2.075	Highly Destabilizing	0.901	D	0.777	deleterious	N	0.453122896	None	None	I
V/H	0.9589	likely_pathogenic	0.9795	pathogenic	-1.63	Destabilizing	0.989	D	0.793	deleterious	None	None	None	None	I
V/I	0.0839	likely_benign	0.0965	benign	-0.615	Destabilizing	0.008	N	0.377	neutral	N	0.412044338	None	None	I
V/K	0.9198	likely_pathogenic	0.9515	pathogenic	-1.255	Destabilizing	0.858	D	0.757	deleterious	None	None	None	None	I
V/L	0.2424	likely_benign	0.2958	benign	-0.615	Destabilizing	0.349	N	0.551	neutral	N	0.294535844	None	None	I
V/M	0.2141	likely_benign	0.2817	benign	-0.516	Destabilizing	0.923	D	0.625	neutral	None	None	None	None	I
V/N	0.7654	likely_pathogenic	0.866	pathogenic	-1.123	Destabilizing	0.923	D	0.822	deleterious	None	None	None	None	I
V/P	0.6439	likely_pathogenic	0.7304	pathogenic	-0.932	Destabilizing	0.961	D	0.791	deleterious	None	None	None	None	I
V/Q	0.8791	likely_pathogenic	0.9324	pathogenic	-1.196	Destabilizing	0.858	D	0.783	deleterious	None	None	None	None	I
V/R	0.8997	likely_pathogenic	0.9355	pathogenic	-0.885	Destabilizing	0.923	D	0.828	deleterious	None	None	None	None	I
V/S	0.5656	likely_pathogenic	0.7001	pathogenic	-1.77	Destabilizing	0.633	D	0.715	prob.delet.	None	None	None	None	I
V/T	0.2841	likely_benign	0.3938	ambiguous	-1.577	Destabilizing	0.044	N	0.425	neutral	None	None	None	None	I
V/W	0.9594	likely_pathogenic	0.9785	pathogenic	-1.363	Destabilizing	0.996	D	0.783	deleterious	None	None	None	None	I
V/Y	0.91	likely_pathogenic	0.9487	pathogenic	-1.052	Destabilizing	0.987	D	0.783	deleterious	None	None	None	None	I

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.