TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25486	76681;76682;76683	chr2:178569676;178569675;178569674	chr2:179434403;179434402;179434401
N2AB	23845	71758;71759;71760	chr2:178569676;178569675;178569674	chr2:179434403;179434402;179434401
N2A	22918	68977;68978;68979	chr2:178569676;178569675;178569674	chr2:179434403;179434402;179434401
N2B	16421	49486;49487;49488	chr2:178569676;178569675;178569674	chr2:179434403;179434402;179434401
Novex-1	16546	49861;49862;49863	chr2:178569676;178569675;178569674	chr2:179434403;179434402;179434401
Novex-2	16613	50062;50063;50064	chr2:178569676;178569675;178569674	chr2:179434403;179434402;179434401
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-73
• Domain position: 82
• Structural Position: 113
• Q(SASA): 0.6824
• Predicted PPI site: I

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
K/N	None	None	0.967	N	0.477	0.241	0.238705975628	gnomAD-4.0.0	1.5937E-06	None	None	None	None	I	None	0	0	None	0	2.78893E-05	None	0	0	0	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
K/A	0.2422	likely_benign	0.2671	benign	0.064	Stabilizing	0.916	D	0.581	neutral	None	None	None	None	I
K/C	0.5945	likely_pathogenic	0.6489	pathogenic	-0.246	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	I
K/D	0.4518	ambiguous	0.4698	ambiguous	-0.217	Destabilizing	0.845	D	0.53	neutral	None	None	None	None	I
K/E	0.1361	likely_benign	0.1442	benign	-0.232	Destabilizing	0.025	N	0.379	neutral	N	0.467628694	None	None	I
K/F	0.7152	likely_pathogenic	0.7515	pathogenic	-0.257	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	I
K/G	0.3694	ambiguous	0.4023	ambiguous	-0.08	Destabilizing	0.916	D	0.495	neutral	None	None	None	None	I
K/H	0.2844	likely_benign	0.3232	benign	-0.235	Destabilizing	0.997	D	0.498	neutral	None	None	None	None	I
K/I	0.2929	likely_benign	0.3242	benign	0.357	Stabilizing	0.983	D	0.631	neutral	N	0.476192249	None	None	I
K/L	0.303	likely_benign	0.3405	ambiguous	0.357	Stabilizing	0.975	D	0.471	neutral	None	None	None	None	I
K/M	0.2153	likely_benign	0.2392	benign	0.089	Stabilizing	0.999	D	0.513	neutral	None	None	None	None	I
K/N	0.35	ambiguous	0.3777	ambiguous	0.207	Stabilizing	0.967	D	0.477	neutral	N	0.514574492	None	None	I
K/P	0.6707	likely_pathogenic	0.6819	pathogenic	0.284	Stabilizing	0.987	D	0.521	neutral	None	None	None	None	I
K/Q	0.1201	likely_benign	0.1331	benign	0.029	Stabilizing	0.935	D	0.484	neutral	N	0.502992061	None	None	I
K/R	0.0768	likely_benign	0.0845	benign	0.016	Stabilizing	0.056	N	0.343	neutral	N	0.460068003	None	None	I
K/S	0.2993	likely_benign	0.3321	benign	-0.182	Destabilizing	0.916	D	0.519	neutral	None	None	None	None	I
K/T	0.154	likely_benign	0.1684	benign	-0.075	Destabilizing	0.967	D	0.473	neutral	N	0.495468656	None	None	I
K/V	0.2575	likely_benign	0.2862	benign	0.284	Stabilizing	0.987	D	0.538	neutral	None	None	None	None	I
K/W	0.7246	likely_pathogenic	0.7669	pathogenic	-0.337	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	I
K/Y	0.5636	ambiguous	0.6043	pathogenic	0.022	Stabilizing	0.996	D	0.593	neutral	None	None	None	None	I

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.