TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14500	43723;43724;43725	chr2:178632396;178632395;178632394	chr2:179497123;179497122;179497121
N2AB	12859	38800;38801;38802	chr2:178632396;178632395;178632394	chr2:179497123;179497122;179497121
N2A	11932	36019;36020;36021	chr2:178632396;178632395;178632394	chr2:179497123;179497122;179497121
N2B	5435	16528;16529;16530	chr2:178632396;178632395;178632394	chr2:179497123;179497122;179497121
Novex-1	5560	16903;16904;16905	chr2:178632396;178632395;178632394	chr2:179497123;179497122;179497121
Novex-2	5627	17104;17105;17106	chr2:178632396;178632395;178632394	chr2:179497123;179497122;179497121
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-96
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3371
• 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
L/F	None	None	0.934	D	0.33	0.465	0.670596422724	gnomAD-4.0.0	1.64681E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.93415E-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
L/A	0.3622	ambiguous	0.3276	benign	-0.984	Destabilizing	0.525	D	0.309	neutral	None	None	None	None	N
L/C	0.6453	likely_pathogenic	0.5911	pathogenic	-0.713	Destabilizing	0.998	D	0.36	neutral	None	None	None	None	N
L/D	0.739	likely_pathogenic	0.7176	pathogenic	-0.182	Destabilizing	0.991	D	0.432	neutral	None	None	None	None	N
L/E	0.409	ambiguous	0.3653	ambiguous	-0.227	Destabilizing	0.974	D	0.419	neutral	None	None	None	None	N
L/F	0.2046	likely_benign	0.1914	benign	-0.664	Destabilizing	0.934	D	0.33	neutral	D	0.534399213	None	None	N
L/G	0.7101	likely_pathogenic	0.667	pathogenic	-1.226	Destabilizing	0.974	D	0.398	neutral	None	None	None	None	N
L/H	0.2741	likely_benign	0.2298	benign	-0.319	Destabilizing	0.997	D	0.409	neutral	D	0.534503061	None	None	N
L/I	0.0757	likely_benign	0.0712	benign	-0.437	Destabilizing	0.002	N	0.081	neutral	N	0.368869092	None	None	N
L/K	0.3481	ambiguous	0.2933	benign	-0.585	Destabilizing	0.974	D	0.379	neutral	None	None	None	None	N
L/M	0.1596	likely_benign	0.1419	benign	-0.421	Destabilizing	0.949	D	0.416	neutral	None	None	None	None	N
L/N	0.4286	ambiguous	0.3921	ambiguous	-0.413	Destabilizing	0.991	D	0.415	neutral	None	None	None	None	N
L/P	0.7556	likely_pathogenic	0.7534	pathogenic	-0.585	Destabilizing	0.989	D	0.428	neutral	D	0.534519713	None	None	N
L/Q	0.2041	likely_benign	0.1633	benign	-0.598	Destabilizing	0.991	D	0.368	neutral	None	None	None	None	N
L/R	0.254	likely_benign	0.2042	benign	0.005	Stabilizing	0.989	D	0.387	neutral	N	0.475048732	None	None	N
L/S	0.3232	likely_benign	0.3037	benign	-0.996	Destabilizing	0.915	D	0.347	neutral	None	None	None	None	N
L/T	0.2737	likely_benign	0.228	benign	-0.926	Destabilizing	0.842	D	0.275	neutral	None	None	None	None	N
L/V	0.1039	likely_benign	0.0928	benign	-0.585	Destabilizing	0.005	N	0.124	neutral	N	0.349863895	None	None	N
L/W	0.4159	ambiguous	0.3872	ambiguous	-0.677	Destabilizing	0.998	D	0.477	neutral	None	None	None	None	N
L/Y	0.4985	ambiguous	0.4648	ambiguous	-0.454	Destabilizing	0.991	D	0.383	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.