TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22660	68203;68204;68205	chr2:178579052;178579051;178579050	chr2:179443779;179443778;179443777
N2AB	21019	63280;63281;63282	chr2:178579052;178579051;178579050	chr2:179443779;179443778;179443777
N2A	20092	60499;60500;60501	chr2:178579052;178579051;178579050	chr2:179443779;179443778;179443777
N2B	13595	41008;41009;41010	chr2:178579052;178579051;178579050	chr2:179443779;179443778;179443777
Novex-1	13720	41383;41384;41385	chr2:178579052;178579051;178579050	chr2:179443779;179443778;179443777
Novex-2	13787	41584;41585;41586	chr2:178579052;178579051;178579050	chr2:179443779;179443778;179443777
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-52
• Domain position: 18
• Structural Position: 19
• Q(SASA): 0.0972
• 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
A/T	None	None	0.999	N	0.653	0.296	0.301455362545	gnomAD-4.0.0	1.59239E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86007E-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
A/C	0.4172	ambiguous	0.4231	ambiguous	-1.592	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
A/D	0.6118	likely_pathogenic	0.6027	pathogenic	-2.606	Highly Destabilizing	0.999	D	0.806	deleterious	N	0.488081324	None	None	N
A/E	0.5554	ambiguous	0.5463	ambiguous	-2.589	Highly Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
A/F	0.3563	ambiguous	0.3431	ambiguous	-1.188	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
A/G	0.1035	likely_benign	0.0973	benign	-1.389	Destabilizing	0.244	N	0.279	neutral	N	0.412930204	None	None	N
A/H	0.5801	likely_pathogenic	0.5935	pathogenic	-1.332	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
A/I	0.5507	ambiguous	0.4788	ambiguous	-0.515	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
A/K	0.8407	likely_pathogenic	0.8266	pathogenic	-1.357	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
A/L	0.3912	ambiguous	0.347	ambiguous	-0.515	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
A/M	0.3148	likely_benign	0.2789	benign	-0.636	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/N	0.3527	ambiguous	0.3344	benign	-1.444	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
A/P	0.9824	likely_pathogenic	0.9775	pathogenic	-0.681	Destabilizing	1.0	D	0.803	deleterious	N	0.476243857	None	None	N
A/Q	0.5422	ambiguous	0.5333	ambiguous	-1.636	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
A/R	0.7697	likely_pathogenic	0.7736	pathogenic	-0.986	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
A/S	0.0865	likely_benign	0.0867	benign	-1.709	Destabilizing	0.996	D	0.481	neutral	N	0.386447318	None	None	N
A/T	0.1419	likely_benign	0.1276	benign	-1.612	Destabilizing	0.999	D	0.653	neutral	N	0.423336412	None	None	N
A/V	0.2959	likely_benign	0.2496	benign	-0.681	Destabilizing	1.0	D	0.592	neutral	N	0.473709304	None	None	N
A/W	0.8147	likely_pathogenic	0.8262	pathogenic	-1.566	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
A/Y	0.4753	ambiguous	0.4886	ambiguous	-1.152	Destabilizing	1.0	D	0.845	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.