TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8582	25969;25970;25971	chr2:178715670;178715669;178715668	chr2:179580397;179580396;179580395
N2AB	8265	25018;25019;25020	chr2:178715670;178715669;178715668	chr2:179580397;179580396;179580395
N2A	7338	22237;22238;22239	chr2:178715670;178715669;178715668	chr2:179580397;179580396;179580395
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-71
• Domain position: 34
• Structural Position: 47
• Q(SASA): 0.2553
• 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/S	None	None	0.123	N	0.469	0.22	0.585261766934	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
L/V	rs1420202972	-1.593	None	N	0.219	0.094	0.245101548738	gnomAD-2.1.1	7.18E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.57E-05	0
L/V	rs1420202972	-1.593	None	N	0.219	0.094	0.245101548738	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/V	rs1420202972	-1.593	None	N	0.219	0.094	0.245101548738	gnomAD-4.0.0	2.56512E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.79067E-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	0.117	likely_benign	0.1093	benign	-2.199	Highly Destabilizing	0.495	N	0.483	neutral	None	None	None	None	N
L/C	0.2786	likely_benign	0.281	benign	-0.959	Destabilizing	0.997	D	0.545	neutral	None	None	None	None	N
L/D	0.3665	ambiguous	0.3389	benign	-2.2	Highly Destabilizing	0.943	D	0.617	neutral	None	None	None	None	N
L/E	0.1763	likely_benign	0.1654	benign	-2.106	Highly Destabilizing	0.925	D	0.621	neutral	None	None	None	None	N
L/F	0.0773	likely_benign	0.08	benign	-1.479	Destabilizing	0.833	D	0.525	neutral	N	0.503563356	None	None	N
L/G	0.3011	likely_benign	0.2868	benign	-2.59	Highly Destabilizing	0.826	D	0.589	neutral	None	None	None	None	N
L/H	0.0865	likely_benign	0.0822	benign	-1.888	Destabilizing	0.994	D	0.635	neutral	None	None	None	None	N
L/I	0.0631	likely_benign	0.0623	benign	-1.122	Destabilizing	0.001	N	0.337	neutral	N	0.447093998	None	None	N
L/K	0.1071	likely_benign	0.0997	benign	-1.592	Destabilizing	0.123	N	0.595	neutral	None	None	None	None	N
L/M	0.0812	likely_benign	0.0809	benign	-0.678	Destabilizing	0.801	D	0.549	neutral	None	None	None	None	N
L/N	0.1634	likely_benign	0.1483	benign	-1.507	Destabilizing	0.943	D	0.621	neutral	None	None	None	None	N
L/P	0.8457	likely_pathogenic	0.8435	pathogenic	-1.459	Destabilizing	0.971	D	0.621	neutral	None	None	None	None	N
L/Q	0.0712	likely_benign	0.0688	benign	-1.607	Destabilizing	0.933	D	0.591	neutral	None	None	None	None	N
L/R	0.0732	likely_benign	0.069	benign	-1.019	Destabilizing	0.931	D	0.599	neutral	None	None	None	None	N
L/S	0.1048	likely_benign	0.0964	benign	-2.062	Highly Destabilizing	0.123	N	0.469	neutral	N	0.446010989	None	None	N
L/T	0.0818	likely_benign	0.0753	benign	-1.862	Destabilizing	0.008	N	0.267	neutral	None	None	None	None	N
L/V	0.06	likely_benign	0.0608	benign	-1.459	Destabilizing	None	N	0.219	neutral	N	0.422254269	None	None	N
L/W	0.1242	likely_benign	0.1306	benign	-1.74	Destabilizing	0.998	D	0.632	neutral	None	None	None	None	N
L/Y	0.1795	likely_benign	0.1748	benign	-1.499	Destabilizing	0.612	D	0.557	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.