TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5641	17146;17147;17148	chr2:178731954;178731953;178731952	chr2:179596681;179596680;179596679
N2AB	5324	16195;16196;16197	chr2:178731954;178731953;178731952	chr2:179596681;179596680;179596679
N2A	4397	13414;13415;13416	chr2:178731954;178731953;178731952	chr2:179596681;179596680;179596679
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-40
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.7034
• 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/T	None	None	0.062	N	0.365	0.27	0.316198179892	gnomAD-4.0.0	1.60697E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.89712E-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
K/A	0.2142	likely_benign	0.218	benign	-0.068	Destabilizing	0.035	N	0.381	neutral	None	None	None	None	I
K/C	0.5929	likely_pathogenic	0.6369	pathogenic	-0.31	Destabilizing	0.824	D	0.417	neutral	None	None	None	None	I
K/D	0.3729	ambiguous	0.3868	ambiguous	0.199	Stabilizing	0.081	N	0.374	neutral	None	None	None	None	I
K/E	0.0957	likely_benign	0.0998	benign	0.242	Stabilizing	0.062	N	0.409	neutral	N	0.508411816	None	None	I
K/F	0.7297	likely_pathogenic	0.7626	pathogenic	-0.093	Destabilizing	0.555	D	0.407	neutral	None	None	None	None	I
K/G	0.2831	likely_benign	0.3052	benign	-0.321	Destabilizing	0.081	N	0.427	neutral	None	None	None	None	I
K/H	0.2485	likely_benign	0.2636	benign	-0.521	Destabilizing	0.824	D	0.35	neutral	None	None	None	None	I
K/I	0.339	likely_benign	0.3771	ambiguous	0.533	Stabilizing	0.235	N	0.415	neutral	None	None	None	None	I
K/L	0.3158	likely_benign	0.3469	ambiguous	0.533	Stabilizing	0.081	N	0.429	neutral	None	None	None	None	I
K/M	0.2033	likely_benign	0.2235	benign	0.22	Stabilizing	0.484	N	0.347	neutral	N	0.487822831	None	None	I
K/N	0.2547	likely_benign	0.2622	benign	0.102	Stabilizing	0.062	N	0.348	neutral	N	0.484669279	None	None	I
K/P	0.8256	likely_pathogenic	0.8485	pathogenic	0.363	Stabilizing	0.38	N	0.366	neutral	None	None	None	None	I
K/Q	0.0982	likely_benign	0.0991	benign	-0.016	Destabilizing	0.004	N	0.233	neutral	N	0.501944416	None	None	I
K/R	0.0739	likely_benign	0.0757	benign	-0.084	Destabilizing	0.001	N	0.228	neutral	N	0.463524888	None	None	I
K/S	0.2416	likely_benign	0.2386	benign	-0.452	Destabilizing	0.001	N	0.211	neutral	None	None	None	None	I
K/T	0.1178	likely_benign	0.1212	benign	-0.237	Destabilizing	0.062	N	0.365	neutral	N	0.515529789	None	None	I
K/V	0.2562	likely_benign	0.2845	benign	0.363	Stabilizing	0.005	N	0.265	neutral	None	None	None	None	I
K/W	0.6623	likely_pathogenic	0.7117	pathogenic	-0.07	Destabilizing	0.935	D	0.488	neutral	None	None	None	None	I
K/Y	0.5493	ambiguous	0.5986	pathogenic	0.264	Stabilizing	0.555	D	0.406	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.