TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8283	25072;25073;25074	chr2:178718159;178718158;178718157	chr2:179582886;179582885;179582884
N2AB	7966	24121;24122;24123	chr2:178718159;178718158;178718157	chr2:179582886;179582885;179582884
N2A	7039	21340;21341;21342	chr2:178718159;178718158;178718157	chr2:179582886;179582885;179582884
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-68
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.137
• 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/F	rs1454021604	None	0.429	D	0.333	0.465	0.328222422547	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/F	rs1454021604	None	0.429	D	0.333	0.465	0.328222422547	gnomAD-4.0.0	3.73346E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08646E-06	0	0
L/V	rs1408912599	None	0.959	D	0.663	0.64	0.738333703548	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/V	rs1408912599	None	0.959	D	0.663	0.64	0.738333703548	gnomAD-4.0.0	6.57151E-06	None	None	None	None	N	None	2.41266E-05	0	None	0	0	None	0	0	0	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	0.9383	likely_pathogenic	0.9595	pathogenic	-2.487	Highly Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
L/C	0.9378	likely_pathogenic	0.9488	pathogenic	-1.785	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
L/D	0.9982	likely_pathogenic	0.999	pathogenic	-3.0	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
L/E	0.9893	likely_pathogenic	0.9938	pathogenic	-2.689	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
L/F	0.1026	likely_benign	0.0831	benign	-1.427	Destabilizing	0.429	N	0.333	neutral	D	0.534938589	None	None	N
L/G	0.9837	likely_pathogenic	0.9904	pathogenic	-3.101	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/H	0.9364	likely_pathogenic	0.9572	pathogenic	-2.673	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
L/I	0.1928	likely_benign	0.174	benign	-0.664	Destabilizing	0.947	D	0.628	neutral	D	0.562404134	None	None	N
L/K	0.9749	likely_pathogenic	0.9847	pathogenic	-1.894	Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
L/M	0.2498	likely_benign	0.2444	benign	-0.776	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
L/N	0.9912	likely_pathogenic	0.9947	pathogenic	-2.491	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
L/P	0.9887	likely_pathogenic	0.9945	pathogenic	-1.259	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
L/Q	0.9376	likely_pathogenic	0.9638	pathogenic	-2.182	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/R	0.9417	likely_pathogenic	0.9633	pathogenic	-1.935	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/S	0.9798	likely_pathogenic	0.988	pathogenic	-3.156	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.654491343	None	None	N
L/T	0.9625	likely_pathogenic	0.9767	pathogenic	-2.671	Highly Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
L/V	0.2984	likely_benign	0.315	benign	-1.259	Destabilizing	0.959	D	0.663	neutral	D	0.611723045	None	None	N
L/W	0.5637	ambiguous	0.6116	pathogenic	-1.806	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/Y	0.7433	likely_pathogenic	0.7319	pathogenic	-1.516	Destabilizing	0.985	D	0.782	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.