TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14277	43054;43055;43056	chr2:178633530;178633529;178633528	chr2:179498257;179498256;179498255
N2AB	12636	38131;38132;38133	chr2:178633530;178633529;178633528	chr2:179498257;179498256;179498255
N2A	11709	35350;35351;35352	chr2:178633530;178633529;178633528	chr2:179498257;179498256;179498255
N2B	5212	15859;15860;15861	chr2:178633530;178633529;178633528	chr2:179498257;179498256;179498255
Novex-1	5337	16234;16235;16236	chr2:178633530;178633529;178633528	chr2:179498257;179498256;179498255
Novex-2	5404	16435;16436;16437	chr2:178633530;178633529;178633528	chr2:179498257;179498256;179498255
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-93
• Domain position: 47
• Structural Position: 123
• Q(SASA): 0.2479
• 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
I/F	rs397517568	-1.403	0.497	D	0.563	0.233	0.439975540334	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	8.9E-06	0
I/F	rs397517568	-1.403	0.497	D	0.563	0.233	0.439975540334	gnomAD-4.0.0	7.52811E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.87413E-05	0	8.99596E-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
I/A	0.562	ambiguous	0.4352	ambiguous	-2.0	Highly Destabilizing	0.072	N	0.59	neutral	None	None	None	None	N
I/C	0.7916	likely_pathogenic	0.7336	pathogenic	-1.225	Destabilizing	0.909	D	0.634	neutral	None	None	None	None	N
I/D	0.9234	likely_pathogenic	0.8815	pathogenic	-1.633	Destabilizing	0.726	D	0.721	prob.delet.	None	None	None	None	N
I/E	0.7756	likely_pathogenic	0.6914	pathogenic	-1.486	Destabilizing	0.726	D	0.717	prob.delet.	None	None	None	None	N
I/F	0.1876	likely_benign	0.1605	benign	-1.168	Destabilizing	0.497	N	0.563	neutral	D	0.534460936	None	None	N
I/G	0.8304	likely_pathogenic	0.7437	pathogenic	-2.465	Highly Destabilizing	0.726	D	0.713	prob.delet.	None	None	None	None	N
I/H	0.743	likely_pathogenic	0.6865	pathogenic	-1.717	Destabilizing	0.968	D	0.721	prob.delet.	None	None	None	None	N
I/K	0.6691	likely_pathogenic	0.5678	pathogenic	-1.434	Destabilizing	0.726	D	0.717	prob.delet.	None	None	None	None	N
I/L	0.1286	likely_benign	0.1114	benign	-0.714	Destabilizing	0.009	N	0.336	neutral	N	0.511965635	None	None	N
I/M	0.1067	likely_benign	0.0967	benign	-0.601	Destabilizing	0.055	N	0.387	neutral	N	0.514793076	None	None	N
I/N	0.6179	likely_pathogenic	0.5023	ambiguous	-1.532	Destabilizing	0.859	D	0.73	prob.delet.	D	0.744178603	None	None	N
I/P	0.9249	likely_pathogenic	0.8829	pathogenic	-1.117	Destabilizing	0.89	D	0.728	prob.delet.	None	None	None	None	N
I/Q	0.6214	likely_pathogenic	0.549	ambiguous	-1.496	Destabilizing	0.726	D	0.729	prob.delet.	None	None	None	None	N
I/R	0.5886	likely_pathogenic	0.4701	ambiguous	-1.067	Destabilizing	0.726	D	0.73	prob.delet.	None	None	None	None	N
I/S	0.5625	ambiguous	0.4478	ambiguous	-2.24	Highly Destabilizing	0.497	N	0.648	neutral	D	0.660993695	None	None	N
I/T	0.4955	ambiguous	0.3688	ambiguous	-1.951	Destabilizing	0.124	N	0.608	neutral	D	0.613560662	None	None	N
I/V	0.0898	likely_benign	0.0766	benign	-1.117	Destabilizing	None	N	0.181	neutral	D	0.525720041	None	None	N
I/W	0.8382	likely_pathogenic	0.8098	pathogenic	-1.407	Destabilizing	0.968	D	0.737	prob.delet.	None	None	None	None	N
I/Y	0.6006	likely_pathogenic	0.5398	ambiguous	-1.115	Destabilizing	0.726	D	0.651	neutral	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.