TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28651	86176;86177;86178	chr2:178560181;178560180;178560179	chr2:179424908;179424907;179424906
N2AB	27010	81253;81254;81255	chr2:178560181;178560180;178560179	chr2:179424908;179424907;179424906
N2A	26083	78472;78473;78474	chr2:178560181;178560180;178560179	chr2:179424908;179424907;179424906
N2B	19586	58981;58982;58983	chr2:178560181;178560180;178560179	chr2:179424908;179424907;179424906
Novex-1	19711	59356;59357;59358	chr2:178560181;178560180;178560179	chr2:179424908;179424907;179424906
Novex-2	19778	59557;59558;59559	chr2:178560181;178560180;178560179	chr2:179424908;179424907;179424906
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-97
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.5438
• 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
L/P	None	None	1.0	N	0.775	0.442	0.753645140278	gnomAD-4.0.0	1.36842E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79894E-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
L/A	0.2387	likely_benign	0.2091	benign	-0.759	Destabilizing	0.998	D	0.69	prob.delet.	None	None	None	None	I
L/C	0.4824	ambiguous	0.4452	ambiguous	-0.689	Destabilizing	1.0	D	0.657	prob.neutral	None	None	None	None	I
L/D	0.784	likely_pathogenic	0.7479	pathogenic	0.12	Stabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
L/E	0.3918	ambiguous	0.3475	ambiguous	0.039	Stabilizing	0.999	D	0.785	deleterious	None	None	None	None	I
L/F	0.2032	likely_benign	0.1897	benign	-0.734	Destabilizing	0.999	D	0.693	prob.delet.	None	None	None	None	I
L/G	0.6403	likely_pathogenic	0.5891	pathogenic	-0.932	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	I
L/H	0.2629	likely_benign	0.2318	benign	-0.205	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
L/I	0.1066	likely_benign	0.0888	benign	-0.423	Destabilizing	0.997	D	0.499	neutral	N	0.463758883	None	None	I
L/K	0.2542	likely_benign	0.2191	benign	-0.242	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	I
L/M	0.1469	likely_benign	0.1368	benign	-0.379	Destabilizing	0.999	D	0.692	prob.delet.	None	None	None	None	I
L/N	0.497	ambiguous	0.4427	ambiguous	-0.054	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
L/P	0.1256	likely_benign	0.1193	benign	-0.501	Destabilizing	1.0	D	0.775	deleterious	N	0.341488607	None	None	I
L/Q	0.1621	likely_benign	0.1396	benign	-0.285	Destabilizing	1.0	D	0.771	deleterious	N	0.473245157	None	None	I
L/R	0.2155	likely_benign	0.1818	benign	0.267	Stabilizing	0.999	D	0.797	deleterious	N	0.452080451	None	None	I
L/S	0.2848	likely_benign	0.2462	benign	-0.611	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	I
L/T	0.2217	likely_benign	0.1825	benign	-0.582	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	I
L/V	0.1029	likely_benign	0.0876	benign	-0.501	Destabilizing	0.997	D	0.517	neutral	N	0.414386068	None	None	I
L/W	0.4403	ambiguous	0.3947	ambiguous	-0.706	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
L/Y	0.4173	ambiguous	0.4023	ambiguous	-0.443	Destabilizing	0.999	D	0.687	prob.delet.	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.