TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35671	107236;107237;107238	chr2:178528740;178528739;178528738	chr2:179393467;179393466;179393465
N2AB	34030	102313;102314;102315	chr2:178528740;178528739;178528738	chr2:179393467;179393466;179393465
N2A	33103	99532;99533;99534	chr2:178528740;178528739;178528738	chr2:179393467;179393466;179393465
N2B	26606	80041;80042;80043	chr2:178528740;178528739;178528738	chr2:179393467;179393466;179393465
Novex-1	26731	80416;80417;80418	chr2:178528740;178528739;178528738	chr2:179393467;179393466;179393465
Novex-2	26798	80617;80618;80619	chr2:178528740;178528739;178528738	chr2:179393467;179393466;179393465
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-167
• Domain position: 65
• Structural Position: 149
• Q(SASA): 0.2901
• 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
D/N	rs1397922467	-0.512	0.117	N	0.629	0.409	0.37953744168	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
D/N	rs1397922467	-0.512	0.117	N	0.629	0.409	0.37953744168	gnomAD-4.0.0	2.05345E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69938E-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
D/A	0.7122	likely_pathogenic	0.6433	pathogenic	0.746	Stabilizing	0.062	N	0.8	deleterious	N	0.514817356	None	None	N
D/C	0.9325	likely_pathogenic	0.9208	pathogenic	0.518	Stabilizing	0.935	D	0.851	deleterious	None	None	None	None	N
D/E	0.4539	ambiguous	0.4325	ambiguous	-0.283	Destabilizing	None	N	0.293	neutral	N	0.514084423	None	None	N
D/F	0.9436	likely_pathogenic	0.9259	pathogenic	1.501	Stabilizing	0.555	D	0.86	deleterious	None	None	None	None	N
D/G	0.7462	likely_pathogenic	0.676	pathogenic	0.325	Stabilizing	0.117	N	0.723	prob.delet.	N	0.514939512	None	None	N
D/H	0.7023	likely_pathogenic	0.6226	pathogenic	1.39	Stabilizing	None	N	0.517	neutral	N	0.491856386	None	None	N
D/I	0.8739	likely_pathogenic	0.8267	pathogenic	1.858	Stabilizing	0.555	D	0.859	deleterious	None	None	None	None	N
D/K	0.8766	likely_pathogenic	0.8315	pathogenic	0.942	Stabilizing	0.081	N	0.719	prob.delet.	None	None	None	None	N
D/L	0.8758	likely_pathogenic	0.8368	pathogenic	1.858	Stabilizing	0.38	N	0.84	deleterious	None	None	None	None	N
D/M	0.9434	likely_pathogenic	0.9247	pathogenic	1.91	Stabilizing	0.935	D	0.84	deleterious	None	None	None	None	N
D/N	0.4375	ambiguous	0.3612	ambiguous	-0.072	Destabilizing	0.117	N	0.629	neutral	N	0.513840112	None	None	N
D/P	0.9875	likely_pathogenic	0.9827	pathogenic	1.518	Stabilizing	0.555	D	0.749	deleterious	None	None	None	None	N
D/Q	0.8392	likely_pathogenic	0.803	pathogenic	0.241	Stabilizing	0.081	N	0.649	neutral	None	None	None	None	N
D/R	0.9224	likely_pathogenic	0.8961	pathogenic	0.985	Stabilizing	0.235	N	0.829	deleterious	None	None	None	None	N
D/S	0.6408	likely_pathogenic	0.5636	ambiguous	-0.22	Destabilizing	0.081	N	0.632	neutral	None	None	None	None	N
D/T	0.8039	likely_pathogenic	0.7487	pathogenic	0.187	Stabilizing	0.149	N	0.761	deleterious	None	None	None	None	N
D/V	0.7332	likely_pathogenic	0.6656	pathogenic	1.518	Stabilizing	0.317	N	0.84	deleterious	N	0.515183823	None	None	N
D/W	0.9838	likely_pathogenic	0.9805	pathogenic	1.614	Stabilizing	0.935	D	0.85	deleterious	None	None	None	None	N
D/Y	0.6923	likely_pathogenic	0.6346	pathogenic	1.831	Stabilizing	0.317	N	0.859	deleterious	N	0.515061668	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.