TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33056	99391;99392;99393	chr2:178538663;178538662;178538661	chr2:179403390;179403389;179403388
N2AB	31415	94468;94469;94470	chr2:178538663;178538662;178538661	chr2:179403390;179403389;179403388
N2A	30488	91687;91688;91689	chr2:178538663;178538662;178538661	chr2:179403390;179403389;179403388
N2B	23991	72196;72197;72198	chr2:178538663;178538662;178538661	chr2:179403390;179403389;179403388
Novex-1	24116	72571;72572;72573	chr2:178538663;178538662;178538661	chr2:179403390;179403389;179403388
Novex-2	24183	72772;72773;72774	chr2:178538663;178538662;178538661	chr2:179403390;179403389;179403388
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: Fn3-129
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.5387
• 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
K/N	rs1692876127	None	0.117	N	0.478	0.113	0.0666544352282	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
K/N	rs1692876127	None	0.117	N	0.478	0.113	0.0666544352282	gnomAD-4.0.0	6.57341E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07211E-04	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	0.3352	likely_benign	0.4533	ambiguous	-0.887	Destabilizing	0.067	N	0.491	neutral	None	None	None	None	N
K/C	0.3256	likely_benign	0.5056	ambiguous	-0.952	Destabilizing	0.935	D	0.668	neutral	None	None	None	None	N
K/D	0.5689	likely_pathogenic	0.7081	pathogenic	-1.075	Destabilizing	0.149	N	0.551	neutral	None	None	None	None	N
K/E	0.2035	likely_benign	0.2694	benign	-0.852	Destabilizing	0.027	N	0.507	neutral	N	0.455350043	None	None	N
K/F	0.655	likely_pathogenic	0.7904	pathogenic	-0.215	Destabilizing	0.555	D	0.643	neutral	None	None	None	None	N
K/G	0.2503	likely_benign	0.3884	ambiguous	-1.333	Destabilizing	0.149	N	0.587	neutral	None	None	None	None	N
K/H	0.2133	likely_benign	0.3205	benign	-1.417	Destabilizing	0.555	D	0.605	neutral	None	None	None	None	N
K/I	0.3493	ambiguous	0.4562	ambiguous	0.334	Stabilizing	0.555	D	0.649	neutral	None	None	None	None	N
K/L	0.2507	likely_benign	0.3418	ambiguous	0.334	Stabilizing	0.149	N	0.587	neutral	None	None	None	None	N
K/M	0.2106	likely_benign	0.2763	benign	-0.023	Destabilizing	0.741	D	0.611	neutral	N	0.48165121	None	None	N
K/N	0.3835	ambiguous	0.497	ambiguous	-1.325	Destabilizing	0.117	N	0.478	neutral	N	0.392261357	None	None	N
K/P	0.4883	ambiguous	0.6599	pathogenic	-0.047	Destabilizing	0.555	D	0.597	neutral	None	None	None	None	N
K/Q	0.1013	likely_benign	0.138	benign	-1.108	Destabilizing	0.062	N	0.504	neutral	N	0.451405661	None	None	N
K/R	0.0521	likely_benign	0.0602	benign	-0.909	Destabilizing	None	N	0.281	neutral	N	0.438591079	None	None	N
K/S	0.3443	ambiguous	0.4796	ambiguous	-1.819	Destabilizing	0.149	N	0.495	neutral	None	None	None	None	N
K/T	0.1518	likely_benign	0.189	benign	-1.362	Destabilizing	0.117	N	0.515	neutral	N	0.346043491	None	None	N
K/V	0.3368	likely_benign	0.4365	ambiguous	-0.047	Destabilizing	0.149	N	0.619	neutral	None	None	None	None	N
K/W	0.4581	ambiguous	0.6897	pathogenic	-0.253	Destabilizing	0.935	D	0.673	neutral	None	None	None	None	N
K/Y	0.4805	ambiguous	0.6333	pathogenic	0.054	Stabilizing	0.555	D	0.651	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.