TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31146	93661;93662;93663	chr2:178548190;178548189;178548188	chr2:179412917;179412916;179412915
N2AB	29505	88738;88739;88740	chr2:178548190;178548189;178548188	chr2:179412917;179412916;179412915
N2A	28578	85957;85958;85959	chr2:178548190;178548189;178548188	chr2:179412917;179412916;179412915
N2B	22081	66466;66467;66468	chr2:178548190;178548189;178548188	chr2:179412917;179412916;179412915
Novex-1	22206	66841;66842;66843	chr2:178548190;178548189;178548188	chr2:179412917;179412916;179412915
Novex-2	22273	67042;67043;67044	chr2:178548190;178548189;178548188	chr2:179412917;179412916;179412915
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-115
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.3004
• 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
T/I	None	None	0.896	N	0.391	0.269	0.390220360785	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
T/S	None	None	0.016	D	0.142	0.113	0.19670166235	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
T/A	0.0982	likely_benign	0.105	benign	-0.658	Destabilizing	0.201	N	0.453	neutral	N	0.489805889	None	None	I
T/C	0.3533	ambiguous	0.409	ambiguous	-0.42	Destabilizing	0.992	D	0.431	neutral	None	None	None	None	I
T/D	0.5024	ambiguous	0.4416	ambiguous	0.125	Stabilizing	0.617	D	0.379	neutral	None	None	None	None	I
T/E	0.4006	ambiguous	0.3622	ambiguous	0.075	Stabilizing	0.617	D	0.387	neutral	None	None	None	None	I
T/F	0.3005	likely_benign	0.303	benign	-0.911	Destabilizing	0.92	D	0.493	neutral	None	None	None	None	I
T/G	0.2451	likely_benign	0.2464	benign	-0.844	Destabilizing	0.447	N	0.463	neutral	None	None	None	None	I
T/H	0.3024	likely_benign	0.285	benign	-1.083	Destabilizing	0.92	D	0.483	neutral	None	None	None	None	I
T/I	0.153	likely_benign	0.1852	benign	-0.272	Destabilizing	0.896	D	0.391	neutral	N	0.51375056	None	None	I
T/K	0.2393	likely_benign	0.2309	benign	-0.582	Destabilizing	0.447	N	0.435	neutral	None	None	None	None	I
T/L	0.0969	likely_benign	0.1154	benign	-0.272	Destabilizing	0.617	D	0.408	neutral	None	None	None	None	I
T/M	0.0965	likely_benign	0.1144	benign	-0.004	Destabilizing	0.992	D	0.434	neutral	None	None	None	None	I
T/N	0.147	likely_benign	0.1541	benign	-0.367	Destabilizing	0.379	N	0.406	neutral	N	0.488831611	None	None	I
T/P	0.4028	ambiguous	0.3324	benign	-0.37	Destabilizing	0.896	D	0.384	neutral	D	0.529599251	None	None	I
T/Q	0.2612	likely_benign	0.2538	benign	-0.612	Destabilizing	0.85	D	0.382	neutral	None	None	None	None	I
T/R	0.2084	likely_benign	0.1804	benign	-0.276	Destabilizing	0.005	N	0.161	neutral	None	None	None	None	I
T/S	0.107	likely_benign	0.1094	benign	-0.669	Destabilizing	0.016	N	0.142	neutral	D	0.524562199	None	None	I
T/V	0.1265	likely_benign	0.1541	benign	-0.37	Destabilizing	0.617	D	0.391	neutral	None	None	None	None	I
T/W	0.6447	likely_pathogenic	0.5909	pathogenic	-0.82	Destabilizing	0.992	D	0.591	neutral	None	None	None	None	I
T/Y	0.3681	ambiguous	0.35	ambiguous	-0.595	Destabilizing	0.972	D	0.495	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.