TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35641	107146;107147;107148	chr2:178528830;178528829;178528828	chr2:179393557;179393556;179393555
N2AB	34000	102223;102224;102225	chr2:178528830;178528829;178528828	chr2:179393557;179393556;179393555
N2A	33073	99442;99443;99444	chr2:178528830;178528829;178528828	chr2:179393557;179393556;179393555
N2B	26576	79951;79952;79953	chr2:178528830;178528829;178528828	chr2:179393557;179393556;179393555
Novex-1	26701	80326;80327;80328	chr2:178528830;178528829;178528828	chr2:179393557;179393556;179393555
Novex-2	26768	80527;80528;80529	chr2:178528830;178528829;178528828	chr2:179393557;179393556;179393555
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-167
• Domain position: 35
• Structural Position: 51
• Q(SASA): 0.9109
• 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
N/H	None	None	0.999	N	0.633	0.371	0.302459207581	gnomAD-4.0.0	2.73661E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59761E-06	0	0
N/K	None	None	0.117	N	0.425	0.077	0.110078149338	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	2.75482E-04	None	0	0	3.9375E-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
N/A	0.734	likely_pathogenic	0.7867	pathogenic	-0.391	Destabilizing	0.983	D	0.571	neutral	None	None	None	None	I
N/C	0.7905	likely_pathogenic	0.8199	pathogenic	0.27	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
N/D	0.2434	likely_benign	0.2866	benign	0.345	Stabilizing	0.977	D	0.605	neutral	N	0.460998218	None	None	I
N/E	0.8026	likely_pathogenic	0.8441	pathogenic	0.318	Stabilizing	0.966	D	0.613	neutral	None	None	None	None	I
N/F	0.9467	likely_pathogenic	0.9637	pathogenic	-0.735	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
N/G	0.4805	ambiguous	0.5269	ambiguous	-0.569	Destabilizing	0.983	D	0.582	neutral	None	None	None	None	I
N/H	0.3077	likely_benign	0.3529	ambiguous	-0.561	Destabilizing	0.999	D	0.633	neutral	N	0.466892401	None	None	I
N/I	0.9381	likely_pathogenic	0.9557	pathogenic	-0.01	Destabilizing	0.997	D	0.693	prob.neutral	N	0.467239118	None	None	I
N/K	0.6959	likely_pathogenic	0.7476	pathogenic	0.181	Stabilizing	0.117	N	0.425	neutral	N	0.46602561	None	None	I
N/L	0.798	likely_pathogenic	0.8387	pathogenic	-0.01	Destabilizing	0.995	D	0.637	neutral	None	None	None	None	I
N/M	0.8835	likely_pathogenic	0.9133	pathogenic	0.292	Stabilizing	1.0	D	0.623	neutral	None	None	None	None	I
N/P	0.9786	likely_pathogenic	0.9843	pathogenic	-0.11	Destabilizing	0.998	D	0.629	neutral	None	None	None	None	I
N/Q	0.7223	likely_pathogenic	0.7592	pathogenic	-0.336	Destabilizing	0.995	D	0.644	neutral	None	None	None	None	I
N/R	0.6838	likely_pathogenic	0.7226	pathogenic	0.194	Stabilizing	0.99	D	0.609	neutral	None	None	None	None	I
N/S	0.1899	likely_benign	0.2027	benign	-0.167	Destabilizing	0.977	D	0.567	neutral	N	0.466198968	None	None	I
N/T	0.6978	likely_pathogenic	0.7438	pathogenic	-0.039	Destabilizing	0.977	D	0.599	neutral	N	0.466892401	None	None	I
N/V	0.9316	likely_pathogenic	0.9503	pathogenic	-0.11	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	I
N/W	0.966	likely_pathogenic	0.9743	pathogenic	-0.685	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
N/Y	0.5553	ambiguous	0.6019	pathogenic	-0.421	Destabilizing	0.999	D	0.641	neutral	N	0.467239118	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.