TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17774	53545;53546;53547	chr2:178607282;178607281;178607280	chr2:179472009;179472008;179472007
N2AB	16133	48622;48623;48624	chr2:178607282;178607281;178607280	chr2:179472009;179472008;179472007
N2A	15206	45841;45842;45843	chr2:178607282;178607281;178607280	chr2:179472009;179472008;179472007
N2B	8709	26350;26351;26352	chr2:178607282;178607281;178607280	chr2:179472009;179472008;179472007
Novex-1	8834	26725;26726;26727	chr2:178607282;178607281;178607280	chr2:179472009;179472008;179472007
Novex-2	8901	26926;26927;26928	chr2:178607282;178607281;178607280	chr2:179472009;179472008;179472007
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: Fn3-17
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.4261
• 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	rs770511876	-0.903	0.999	N	0.572	0.275	0.433379234345	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/A	rs770511876	-0.903	0.999	N	0.572	0.275	0.433379234345	gnomAD-4.0.0	1.59361E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86185E-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	0.4446	ambiguous	0.5207	ambiguous	-0.799	Destabilizing	0.999	D	0.572	neutral	N	0.504778786	None	None	N
V/C	0.9085	likely_pathogenic	0.9386	pathogenic	-0.777	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/D	0.9086	likely_pathogenic	0.9524	pathogenic	-0.631	Destabilizing	1.0	D	0.836	deleterious	N	0.497756813	None	None	N
V/E	0.791	likely_pathogenic	0.8709	pathogenic	-0.705	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
V/F	0.5403	ambiguous	0.6198	pathogenic	-0.755	Destabilizing	1.0	D	0.797	deleterious	N	0.469883846	None	None	N
V/G	0.6769	likely_pathogenic	0.7595	pathogenic	-0.995	Destabilizing	1.0	D	0.799	deleterious	N	0.49362043	None	None	N
V/H	0.9321	likely_pathogenic	0.9606	pathogenic	-0.433	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/I	0.1051	likely_benign	0.1206	benign	-0.412	Destabilizing	0.997	D	0.47	neutral	N	0.504085352	None	None	N
V/K	0.8689	likely_pathogenic	0.9115	pathogenic	-0.81	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/L	0.4912	ambiguous	0.6006	pathogenic	-0.412	Destabilizing	0.997	D	0.545	neutral	N	0.468009909	None	None	N
V/M	0.3308	likely_benign	0.4296	ambiguous	-0.47	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
V/N	0.7674	likely_pathogenic	0.8376	pathogenic	-0.593	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/P	0.9711	likely_pathogenic	0.9775	pathogenic	-0.505	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
V/Q	0.7552	likely_pathogenic	0.8268	pathogenic	-0.81	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/R	0.8334	likely_pathogenic	0.8756	pathogenic	-0.229	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
V/S	0.5869	likely_pathogenic	0.6801	pathogenic	-0.987	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
V/T	0.3749	ambiguous	0.4526	ambiguous	-0.958	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
V/W	0.9767	likely_pathogenic	0.9865	pathogenic	-0.852	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/Y	0.9084	likely_pathogenic	0.938	pathogenic	-0.581	Destabilizing	1.0	D	0.808	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.