TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15645	47158;47159;47160	chr2:178618617;178618616;178618615	chr2:179483344;179483343;179483342
N2AB	14004	42235;42236;42237	chr2:178618617;178618616;178618615	chr2:179483344;179483343;179483342
N2A	13077	39454;39455;39456	chr2:178618617;178618616;178618615	chr2:179483344;179483343;179483342
N2B	6580	19963;19964;19965	chr2:178618617;178618616;178618615	chr2:179483344;179483343;179483342
Novex-1	6705	20338;20339;20340	chr2:178618617;178618616;178618615	chr2:179483344;179483343;179483342
Novex-2	6772	20539;20540;20541	chr2:178618617;178618616;178618615	chr2:179483344;179483343;179483342
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: Ig-108
• Domain position: 78
• Structural Position: 165
• Q(SASA): 0.6538
• 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/R	rs2057766757	None	0.669	N	0.401	0.177	0.411133732114	gnomAD-4.0.0	3.34922E-05	None	None	None	None	I	None	0	0	None	0	5.83301E-04	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	0.2374	likely_benign	0.3368	benign	-0.297	Destabilizing	0.688	D	0.465	neutral	None	None	None	None	I
K/C	0.5444	ambiguous	0.6757	pathogenic	-0.482	Destabilizing	0.998	D	0.558	neutral	None	None	None	None	I
K/D	0.4903	ambiguous	0.588	pathogenic	-0.019	Destabilizing	0.728	D	0.45	neutral	None	None	None	None	I
K/E	0.126	likely_benign	0.1781	benign	0.041	Stabilizing	0.022	N	0.189	neutral	N	0.47235402	None	None	I
K/F	0.5432	ambiguous	0.6581	pathogenic	-0.135	Destabilizing	0.991	D	0.537	neutral	None	None	None	None	I
K/G	0.3817	ambiguous	0.4967	ambiguous	-0.601	Destabilizing	0.016	N	0.304	neutral	None	None	None	None	I
K/H	0.2353	likely_benign	0.3022	benign	-0.874	Destabilizing	0.974	D	0.508	neutral	None	None	None	None	I
K/I	0.2085	likely_benign	0.2907	benign	0.456	Stabilizing	0.966	D	0.537	neutral	N	0.515046642	None	None	I
K/L	0.231	likely_benign	0.3496	ambiguous	0.456	Stabilizing	0.842	D	0.541	neutral	None	None	None	None	I
K/M	0.1397	likely_benign	0.1985	benign	0.234	Stabilizing	0.993	D	0.507	neutral	None	None	None	None	I
K/N	0.2814	likely_benign	0.3556	ambiguous	-0.217	Destabilizing	0.801	D	0.417	neutral	N	0.513558625	None	None	I
K/P	0.8068	likely_pathogenic	0.8906	pathogenic	0.236	Stabilizing	0.974	D	0.479	neutral	None	None	None	None	I
K/Q	0.0991	likely_benign	0.1299	benign	-0.361	Destabilizing	0.051	N	0.25	neutral	N	0.480734311	None	None	I
K/R	0.0788	likely_benign	0.0906	benign	-0.429	Destabilizing	0.669	D	0.401	neutral	N	0.512787391	None	None	I
K/S	0.2596	likely_benign	0.3529	ambiguous	-0.811	Destabilizing	0.688	D	0.365	neutral	None	None	None	None	I
K/T	0.1057	likely_benign	0.1447	benign	-0.573	Destabilizing	0.801	D	0.509	neutral	N	0.49946633	None	None	I
K/V	0.1905	likely_benign	0.2767	benign	0.236	Stabilizing	0.915	D	0.509	neutral	None	None	None	None	I
K/W	0.6268	likely_pathogenic	0.7441	pathogenic	-0.032	Destabilizing	0.998	D	0.571	neutral	None	None	None	None	I
K/Y	0.4587	ambiguous	0.5635	ambiguous	0.255	Stabilizing	0.991	D	0.535	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.