TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6971	21136;21137;21138	chr2:178724464;178724463;178724462	chr2:179589191;179589190;179589189
N2AB	6654	20185;20186;20187	chr2:178724464;178724463;178724462	chr2:179589191;179589190;179589189
N2A	5727	17404;17405;17406	chr2:178724464;178724463;178724462	chr2:179589191;179589190;179589189
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: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-54
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1197
• 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/A	None	None	0.951	N	0.666	0.546	0.609443766403	gnomAD-4.0.0	1.59241E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86033E-06	0	0
V/M	None	None	0.988	D	0.694	0.487	0.623514155702	gnomAD-4.0.0	1.59247E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43365E-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	0.4129	ambiguous	0.4377	ambiguous	-1.892	Destabilizing	0.951	D	0.666	neutral	N	0.484660669	None	None	N
V/C	0.9715	likely_pathogenic	0.976	pathogenic	-1.288	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
V/D	0.985	likely_pathogenic	0.9885	pathogenic	-2.603	Highly Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
V/E	0.9639	likely_pathogenic	0.969	pathogenic	-2.335	Highly Destabilizing	0.998	D	0.8	deleterious	D	0.572531887	None	None	N
V/F	0.6069	likely_pathogenic	0.6895	pathogenic	-1.048	Destabilizing	0.039	N	0.432	neutral	None	None	None	None	N
V/G	0.7196	likely_pathogenic	0.765	pathogenic	-2.469	Highly Destabilizing	0.998	D	0.806	deleterious	D	0.541886153	None	None	N
V/H	0.991	likely_pathogenic	0.9923	pathogenic	-2.293	Highly Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
V/I	0.1378	likely_benign	0.136	benign	-0.261	Destabilizing	0.864	D	0.573	neutral	None	None	None	None	N
V/K	0.9879	likely_pathogenic	0.989	pathogenic	-1.644	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
V/L	0.6311	likely_pathogenic	0.6476	pathogenic	-0.261	Destabilizing	0.03	N	0.272	neutral	D	0.542495777	None	None	N
V/M	0.5944	likely_pathogenic	0.6036	pathogenic	-0.293	Destabilizing	0.988	D	0.694	prob.neutral	D	0.578861053	None	None	N
V/N	0.9737	likely_pathogenic	0.9764	pathogenic	-2.126	Highly Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
V/P	0.9765	likely_pathogenic	0.9832	pathogenic	-0.779	Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
V/Q	0.9771	likely_pathogenic	0.9793	pathogenic	-1.869	Destabilizing	0.999	D	0.806	deleterious	None	None	None	None	N
V/R	0.9744	likely_pathogenic	0.9781	pathogenic	-1.61	Destabilizing	0.999	D	0.844	deleterious	None	None	None	None	N
V/S	0.837	likely_pathogenic	0.8473	pathogenic	-2.714	Highly Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
V/T	0.5716	likely_pathogenic	0.565	pathogenic	-2.292	Highly Destabilizing	0.984	D	0.709	prob.delet.	None	None	None	None	N
V/W	0.9903	likely_pathogenic	0.9924	pathogenic	-1.645	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/Y	0.952	likely_pathogenic	0.962	pathogenic	-1.196	Destabilizing	0.939	D	0.771	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.