TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28470	85633;85634;85635	chr2:178560724;178560723;178560722	chr2:179425451;179425450;179425449
N2AB	26829	80710;80711;80712	chr2:178560724;178560723;178560722	chr2:179425451;179425450;179425449
N2A	25902	77929;77930;77931	chr2:178560724;178560723;178560722	chr2:179425451;179425450;179425449
N2B	19405	58438;58439;58440	chr2:178560724;178560723;178560722	chr2:179425451;179425450;179425449
Novex-1	19530	58813;58814;58815	chr2:178560724;178560723;178560722	chr2:179425451;179425450;179425449
Novex-2	19597	59014;59015;59016	chr2:178560724;178560723;178560722	chr2:179425451;179425450;179425449
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-95
• Domain position: 21
• Structural Position: 22
• Q(SASA): 0.1083
• 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
L/V	None	None	0.014	N	0.343	0.214	0.287603790349	gnomAD-4.0.0	1.36855E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79893E-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	0.9026	likely_pathogenic	0.8959	pathogenic	-2.414	Highly Destabilizing	0.754	D	0.731	prob.delet.	None	None	None	None	N
L/C	0.8802	likely_pathogenic	0.8604	pathogenic	-1.96	Destabilizing	0.994	D	0.766	deleterious	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9989	pathogenic	-2.891	Highly Destabilizing	0.993	D	0.915	deleterious	None	None	None	None	N
L/E	0.9935	likely_pathogenic	0.9939	pathogenic	-2.584	Highly Destabilizing	0.978	D	0.912	deleterious	None	None	None	None	N
L/F	0.4819	ambiguous	0.4133	ambiguous	-1.487	Destabilizing	0.942	D	0.668	neutral	D	0.527404567	None	None	N
L/G	0.9856	likely_pathogenic	0.9845	pathogenic	-3.035	Highly Destabilizing	0.978	D	0.906	deleterious	None	None	None	None	N
L/H	0.9823	likely_pathogenic	0.9805	pathogenic	-2.824	Highly Destabilizing	0.997	D	0.903	deleterious	D	0.563412494	None	None	N
L/I	0.096	likely_benign	0.0862	benign	-0.578	Destabilizing	0.014	N	0.302	neutral	N	0.47987207	None	None	N
L/K	0.985	likely_pathogenic	0.9862	pathogenic	-1.77	Destabilizing	0.978	D	0.875	deleterious	None	None	None	None	N
L/M	0.3573	ambiguous	0.302	benign	-0.829	Destabilizing	0.956	D	0.641	neutral	None	None	None	None	N
L/N	0.9939	likely_pathogenic	0.994	pathogenic	-2.364	Highly Destabilizing	0.993	D	0.923	deleterious	None	None	None	None	N
L/P	0.9851	likely_pathogenic	0.986	pathogenic	-1.175	Destabilizing	0.99	D	0.919	deleterious	D	0.563412494	None	None	N
L/Q	0.977	likely_pathogenic	0.9755	pathogenic	-2.04	Highly Destabilizing	0.993	D	0.908	deleterious	None	None	None	None	N
L/R	0.9715	likely_pathogenic	0.9704	pathogenic	-1.845	Destabilizing	0.971	D	0.893	deleterious	D	0.563412494	None	None	N
L/S	0.9856	likely_pathogenic	0.9843	pathogenic	-3.044	Highly Destabilizing	0.956	D	0.855	deleterious	None	None	None	None	N
L/T	0.9428	likely_pathogenic	0.9426	pathogenic	-2.56	Highly Destabilizing	0.956	D	0.76	deleterious	None	None	None	None	N
L/V	0.1321	likely_benign	0.1139	benign	-1.175	Destabilizing	0.014	N	0.343	neutral	N	0.479437088	None	None	N
L/W	0.9459	likely_pathogenic	0.9322	pathogenic	-1.924	Destabilizing	0.998	D	0.846	deleterious	None	None	None	None	N
L/Y	0.9474	likely_pathogenic	0.9357	pathogenic	-1.605	Destabilizing	0.978	D	0.758	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.