TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17554	52885;52886;52887	chr2:178608223;178608222;178608221	chr2:179472950;179472949;179472948
N2AB	15913	47962;47963;47964	chr2:178608223;178608222;178608221	chr2:179472950;179472949;179472948
N2A	14986	45181;45182;45183	chr2:178608223;178608222;178608221	chr2:179472950;179472949;179472948
N2B	8489	25690;25691;25692	chr2:178608223;178608222;178608221	chr2:179472950;179472949;179472948
Novex-1	8614	26065;26066;26067	chr2:178608223;178608222;178608221	chr2:179472950;179472949;179472948
Novex-2	8681	26266;26267;26268	chr2:178608223;178608222;178608221	chr2:179472950;179472949;179472948
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-15
• Domain position: 85
• Structural Position: 119
• Q(SASA): 0.8151
• 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
K/N	rs758615635	0.244	1.0	N	0.746	0.317	0.267755039894	gnomAD-2.1.1	4.15E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.45E-05	None	0	0	0
K/N	rs758615635	0.244	1.0	N	0.746	0.317	0.267755039894	gnomAD-4.0.0	1.61373E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.45926E-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
K/A	0.2636	likely_benign	0.246	benign	-0.023	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	I
K/C	0.6686	likely_pathogenic	0.6431	pathogenic	-0.236	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
K/D	0.4342	ambiguous	0.4119	ambiguous	0.037	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
K/E	0.1692	likely_benign	0.1518	benign	0.039	Stabilizing	0.999	D	0.676	prob.neutral	N	0.430937175	None	None	I
K/F	0.7419	likely_pathogenic	0.7055	pathogenic	-0.274	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
K/G	0.4456	ambiguous	0.404	ambiguous	-0.203	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
K/H	0.338	likely_benign	0.3217	benign	-0.445	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	I
K/I	0.2576	likely_benign	0.2392	benign	0.37	Stabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
K/L	0.2957	likely_benign	0.2814	benign	0.37	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	I
K/M	0.2371	likely_benign	0.2157	benign	0.132	Stabilizing	1.0	D	0.639	neutral	N	0.47756053	None	None	I
K/N	0.285	likely_benign	0.2683	benign	0.22	Stabilizing	1.0	D	0.746	deleterious	N	0.470470185	None	None	I
K/P	0.327	likely_benign	0.316	benign	0.266	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
K/Q	0.141	likely_benign	0.1344	benign	0.054	Stabilizing	1.0	D	0.742	deleterious	N	0.49419922	None	None	I
K/R	0.093	likely_benign	0.092	benign	-0.016	Destabilizing	0.999	D	0.635	neutral	N	0.49419922	None	None	I
K/S	0.3372	likely_benign	0.3152	benign	-0.247	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	I
K/T	0.1705	likely_benign	0.1559	benign	-0.102	Destabilizing	1.0	D	0.725	prob.delet.	N	0.514921209	None	None	I
K/V	0.2382	likely_benign	0.2185	benign	0.266	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
K/W	0.8284	likely_pathogenic	0.7917	pathogenic	-0.305	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
K/Y	0.6005	likely_pathogenic	0.5731	pathogenic	0.05	Stabilizing	1.0	D	0.683	prob.neutral	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.