TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27717	83374;83375;83376	chr2:178562983;178562982;178562981	chr2:179427710;179427709;179427708
N2AB	26076	78451;78452;78453	chr2:178562983;178562982;178562981	chr2:179427710;179427709;179427708
N2A	25149	75670;75671;75672	chr2:178562983;178562982;178562981	chr2:179427710;179427709;179427708
N2B	18652	56179;56180;56181	chr2:178562983;178562982;178562981	chr2:179427710;179427709;179427708
Novex-1	18777	56554;56555;56556	chr2:178562983;178562982;178562981	chr2:179427710;179427709;179427708
Novex-2	18844	56755;56756;56757	chr2:178562983;178562982;178562981	chr2:179427710;179427709;179427708
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: Ig-141
• Domain position: 42
• Structural Position: 69
• Q(SASA): 0.516
• 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
T/S	rs757498214	-0.045	0.002	N	0.126	0.084	0.0806252709748	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14705E-04	0	None	0	0	None	0	None	0	0	0
T/S	rs757498214	-0.045	0.002	N	0.126	0.084	0.0806252709748	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
T/S	rs757498214	-0.045	0.002	N	0.126	0.084	0.0806252709748	gnomAD-4.0.0	1.97161E-05	None	None	None	None	N	None	7.23729E-05	0	None	0	0	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
T/A	0.0725	likely_benign	0.0784	benign	-0.481	Destabilizing	0.08	N	0.185	neutral	N	0.472735364	None	None	N
T/C	0.3446	ambiguous	0.3433	ambiguous	-0.286	Destabilizing	0.991	D	0.352	neutral	None	None	None	None	N
T/D	0.3244	likely_benign	0.3185	benign	0.101	Stabilizing	0.209	N	0.343	neutral	None	None	None	None	N
T/E	0.3126	likely_benign	0.3145	benign	0.068	Stabilizing	0.345	N	0.369	neutral	None	None	None	None	N
T/F	0.3497	ambiguous	0.3483	ambiguous	-0.795	Destabilizing	0.965	D	0.375	neutral	None	None	None	None	N
T/G	0.1347	likely_benign	0.1434	benign	-0.677	Destabilizing	0.209	N	0.336	neutral	None	None	None	None	N
T/H	0.25	likely_benign	0.2426	benign	-0.894	Destabilizing	0.901	D	0.372	neutral	None	None	None	None	N
T/I	0.2636	likely_benign	0.2701	benign	-0.071	Destabilizing	0.662	D	0.398	neutral	N	0.503674347	None	None	N
T/K	0.2209	likely_benign	0.2227	benign	-0.473	Destabilizing	0.209	N	0.348	neutral	None	None	None	None	N
T/L	0.1081	likely_benign	0.1127	benign	-0.071	Destabilizing	0.345	N	0.346	neutral	None	None	None	None	N
T/M	0.1135	likely_benign	0.1207	benign	0.009	Stabilizing	0.965	D	0.357	neutral	None	None	None	None	N
T/N	0.102	likely_benign	0.1023	benign	-0.302	Destabilizing	0.005	N	0.144	neutral	N	0.447183559	None	None	N
T/P	0.0756	likely_benign	0.0713	benign	-0.176	Destabilizing	0.001	N	0.219	neutral	N	0.429349947	None	None	N
T/Q	0.2276	likely_benign	0.2293	benign	-0.439	Destabilizing	0.561	D	0.365	neutral	None	None	None	None	N
T/R	0.2003	likely_benign	0.2015	benign	-0.232	Destabilizing	0.002	N	0.184	neutral	None	None	None	None	N
T/S	0.0843	likely_benign	0.0852	benign	-0.533	Destabilizing	0.002	N	0.126	neutral	N	0.430768525	None	None	N
T/V	0.1757	likely_benign	0.1819	benign	-0.176	Destabilizing	0.561	D	0.185	neutral	None	None	None	None	N
T/W	0.618	likely_pathogenic	0.6138	pathogenic	-0.814	Destabilizing	0.991	D	0.39	neutral	None	None	None	None	N
T/Y	0.3433	ambiguous	0.3405	ambiguous	-0.537	Destabilizing	0.965	D	0.379	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.