TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35681	107266;107267;107268	chr2:178528710;178528709;178528708	chr2:179393437;179393436;179393435
N2AB	34040	102343;102344;102345	chr2:178528710;178528709;178528708	chr2:179393437;179393436;179393435
N2A	33113	99562;99563;99564	chr2:178528710;178528709;178528708	chr2:179393437;179393436;179393435
N2B	26616	80071;80072;80073	chr2:178528710;178528709;178528708	chr2:179393437;179393436;179393435
Novex-1	26741	80446;80447;80448	chr2:178528710;178528709;178528708	chr2:179393437;179393436;179393435
Novex-2	26808	80647;80648;80649	chr2:178528710;178528709;178528708	chr2:179393437;179393436;179393435
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-167
• Domain position: 75
• Structural Position: 161
• Q(SASA): 0.2528
• 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
T/S	None	None	0.999	N	0.579	0.264	0.195762928549	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	1.26695E-04	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
T/A	0.301	likely_benign	0.2719	benign	-0.975	Destabilizing	0.999	D	0.551	neutral	N	0.461518293	None	None	I
T/C	0.8769	likely_pathogenic	0.8436	pathogenic	-0.648	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
T/D	0.6817	likely_pathogenic	0.6772	pathogenic	-0.24	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
T/E	0.722	likely_pathogenic	0.7315	pathogenic	-0.242	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	I
T/F	0.777	likely_pathogenic	0.7625	pathogenic	-1.162	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
T/G	0.4698	ambiguous	0.4366	ambiguous	-1.205	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	I
T/H	0.7011	likely_pathogenic	0.6929	pathogenic	-1.56	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
T/I	0.6727	likely_pathogenic	0.6413	pathogenic	-0.451	Destabilizing	1.0	D	0.663	neutral	N	0.462038368	None	None	I
T/K	0.5358	ambiguous	0.557	ambiguous	-0.652	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	I
T/L	0.3688	ambiguous	0.3474	ambiguous	-0.451	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	I
T/M	0.2431	likely_benign	0.2361	benign	-0.084	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
T/N	0.2084	likely_benign	0.2092	benign	-0.572	Destabilizing	1.0	D	0.683	prob.neutral	N	0.447996343	None	None	I
T/P	0.6014	likely_pathogenic	0.6374	pathogenic	-0.596	Destabilizing	1.0	D	0.655	neutral	N	0.46186501	None	None	I
T/Q	0.6091	likely_pathogenic	0.6102	pathogenic	-0.811	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
T/R	0.4862	ambiguous	0.5012	ambiguous	-0.466	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	I
T/S	0.2554	likely_benign	0.2262	benign	-0.9	Destabilizing	0.999	D	0.579	neutral	N	0.460304785	None	None	I
T/V	0.5487	ambiguous	0.5082	ambiguous	-0.596	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	I
T/W	0.9215	likely_pathogenic	0.9147	pathogenic	-1.041	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	I
T/Y	0.7685	likely_pathogenic	0.7659	pathogenic	-0.801	Destabilizing	1.0	D	0.677	prob.neutral	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.