TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23881	71866;71867;71868	chr2:178574491;178574490;178574489	chr2:179439218;179439217;179439216
N2AB	22240	66943;66944;66945	chr2:178574491;178574490;178574489	chr2:179439218;179439217;179439216
N2A	21313	64162;64163;64164	chr2:178574491;178574490;178574489	chr2:179439218;179439217;179439216
N2B	14816	44671;44672;44673	chr2:178574491;178574490;178574489	chr2:179439218;179439217;179439216
Novex-1	14941	45046;45047;45048	chr2:178574491;178574490;178574489	chr2:179439218;179439217;179439216
Novex-2	15008	45247;45248;45249	chr2:178574491;178574490;178574489	chr2:179439218;179439217;179439216
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-61
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.175
• 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
V/A	None	None	0.472	N	0.517	0.239	0.514472708086	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

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
V/A	0.4929	ambiguous	0.4461	ambiguous	-1.187	Destabilizing	0.472	N	0.517	neutral	N	0.513558559	None	None	N
V/C	0.7885	likely_pathogenic	0.7666	pathogenic	-0.626	Destabilizing	0.996	D	0.563	neutral	None	None	None	None	N
V/D	0.933	likely_pathogenic	0.926	pathogenic	-0.955	Destabilizing	0.984	D	0.642	neutral	None	None	None	None	N
V/E	0.8135	likely_pathogenic	0.8049	pathogenic	-0.747	Destabilizing	0.939	D	0.58	neutral	N	0.499582486	None	None	N
V/F	0.4327	ambiguous	0.3936	ambiguous	-0.525	Destabilizing	0.009	N	0.381	neutral	None	None	None	None	N
V/G	0.7003	likely_pathogenic	0.6377	pathogenic	-1.698	Destabilizing	0.939	D	0.612	neutral	N	0.509000888	None	None	N
V/H	0.8896	likely_pathogenic	0.8752	pathogenic	-1.445	Destabilizing	0.996	D	0.631	neutral	None	None	None	None	N
V/I	0.0786	likely_benign	0.0786	benign	0.207	Stabilizing	0.007	N	0.231	neutral	N	0.420648397	None	None	N
V/K	0.8641	likely_pathogenic	0.8474	pathogenic	-0.682	Destabilizing	0.953	D	0.577	neutral	None	None	None	None	N
V/L	0.2342	likely_benign	0.2155	benign	0.207	Stabilizing	0.003	N	0.219	neutral	D	0.524370198	None	None	N
V/M	0.2789	likely_benign	0.2456	benign	0.079	Stabilizing	0.91	D	0.589	neutral	None	None	None	None	N
V/N	0.7734	likely_pathogenic	0.7588	pathogenic	-0.93	Destabilizing	0.984	D	0.659	neutral	None	None	None	None	N
V/P	0.9223	likely_pathogenic	0.9029	pathogenic	-0.226	Destabilizing	0.984	D	0.613	neutral	None	None	None	None	N
V/Q	0.7329	likely_pathogenic	0.705	pathogenic	-0.722	Destabilizing	0.984	D	0.61	neutral	None	None	None	None	N
V/R	0.8139	likely_pathogenic	0.8027	pathogenic	-0.759	Destabilizing	0.953	D	0.661	neutral	None	None	None	None	N
V/S	0.6222	likely_pathogenic	0.5859	pathogenic	-1.618	Destabilizing	0.953	D	0.573	neutral	None	None	None	None	N
V/T	0.5289	ambiguous	0.4903	ambiguous	-1.256	Destabilizing	0.742	D	0.542	neutral	None	None	None	None	N
V/W	0.9588	likely_pathogenic	0.949	pathogenic	-0.979	Destabilizing	0.996	D	0.648	neutral	None	None	None	None	N
V/Y	0.8412	likely_pathogenic	0.8219	pathogenic	-0.497	Destabilizing	0.835	D	0.581	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.