TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25933	78022;78023;78024	chr2:178568335;178568334;178568333	chr2:179433062;179433061;179433060
N2AB	24292	73099;73100;73101	chr2:178568335;178568334;178568333	chr2:179433062;179433061;179433060
N2A	23365	70318;70319;70320	chr2:178568335;178568334;178568333	chr2:179433062;179433061;179433060
N2B	16868	50827;50828;50829	chr2:178568335;178568334;178568333	chr2:179433062;179433061;179433060
Novex-1	16993	51202;51203;51204	chr2:178568335;178568334;178568333	chr2:179433062;179433061;179433060
Novex-2	17060	51403;51404;51405	chr2:178568335;178568334;178568333	chr2:179433062;179433061;179433060
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-76
• Domain position: 44
• Structural Position: 50
• Q(SASA): 0.2734
• 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
T/K	rs1475741583	-0.875	0.142	N	0.309	0.352	0.26547132957	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/K	rs1475741583	-0.875	0.142	N	0.309	0.352	0.26547132957	gnomAD-4.0.0	2.47943E-06	None	None	None	None	N	None	4.00652E-05	0	None	0	0	None	0	0	0	0	1.60174E-05

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	0.199	likely_benign	0.2118	benign	-0.833	Destabilizing	0.919	D	0.516	neutral	N	0.466724617	None	None	N
T/C	0.7198	likely_pathogenic	0.7221	pathogenic	-0.614	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
T/D	0.9176	likely_pathogenic	0.9333	pathogenic	-0.924	Destabilizing	0.991	D	0.585	neutral	None	None	None	None	N
T/E	0.8631	likely_pathogenic	0.8964	pathogenic	-0.925	Destabilizing	0.938	D	0.559	neutral	None	None	None	None	N
T/F	0.8401	likely_pathogenic	0.881	pathogenic	-0.943	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
T/G	0.6274	likely_pathogenic	0.6712	pathogenic	-1.086	Destabilizing	0.991	D	0.631	neutral	None	None	None	None	N
T/H	0.7868	likely_pathogenic	0.8306	pathogenic	-1.381	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
T/I	0.5533	ambiguous	0.5957	pathogenic	-0.246	Destabilizing	0.994	D	0.645	neutral	N	0.467850066	None	None	N
T/K	0.6351	likely_pathogenic	0.7074	pathogenic	-0.906	Destabilizing	0.142	N	0.309	neutral	N	0.483000791	None	None	N
T/L	0.3124	likely_benign	0.3302	benign	-0.246	Destabilizing	0.968	D	0.548	neutral	None	None	None	None	N
T/M	0.2029	likely_benign	0.2215	benign	0.187	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
T/N	0.4849	ambiguous	0.5231	ambiguous	-0.94	Destabilizing	0.991	D	0.619	neutral	None	None	None	None	N
T/P	0.6376	likely_pathogenic	0.7021	pathogenic	-0.41	Destabilizing	0.994	D	0.647	neutral	N	0.502146699	None	None	N
T/Q	0.7018	likely_pathogenic	0.7662	pathogenic	-1.189	Destabilizing	0.991	D	0.638	neutral	None	None	None	None	N
T/R	0.5693	likely_pathogenic	0.6529	pathogenic	-0.563	Destabilizing	0.976	D	0.584	neutral	N	0.469002155	None	None	N
T/S	0.3113	likely_benign	0.3354	benign	-1.135	Destabilizing	0.958	D	0.513	neutral	N	0.492756425	None	None	N
T/V	0.3509	ambiguous	0.3696	ambiguous	-0.41	Destabilizing	0.968	D	0.55	neutral	None	None	None	None	N
T/W	0.9733	likely_pathogenic	0.9821	pathogenic	-0.887	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
T/Y	0.8728	likely_pathogenic	0.905	pathogenic	-0.643	Destabilizing	0.998	D	0.72	prob.delet.	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.