TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4941	15046;15047;15048	chr2:178735625;178735624;178735623	chr2:179600352;179600351;179600350
N2AB	4624	14095;14096;14097	chr2:178735625;178735624;178735623	chr2:179600352;179600351;179600350
N2A	3697	11314;11315;11316	chr2:178735625;178735624;178735623	chr2:179600352;179600351;179600350
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: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-32
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.7936
• 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/T	None	None	1.0	D	0.724	0.467	0.499281839539	gnomAD-4.0.0	1.36856E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31884E-05	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	0.6512	likely_pathogenic	0.6794	pathogenic	-0.749	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
K/C	0.7816	likely_pathogenic	0.7952	pathogenic	-0.843	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/D	0.7503	likely_pathogenic	0.7773	pathogenic	-0.573	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/E	0.321	likely_benign	0.3436	ambiguous	-0.397	Destabilizing	0.999	D	0.695	prob.neutral	D	0.556712042	None	None	N
K/F	0.9171	likely_pathogenic	0.9295	pathogenic	-0.187	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
K/G	0.5372	ambiguous	0.5542	ambiguous	-1.179	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
K/H	0.4474	ambiguous	0.4807	ambiguous	-1.5	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
K/I	0.7407	likely_pathogenic	0.7683	pathogenic	0.402	Stabilizing	1.0	D	0.707	prob.neutral	D	0.696169674	None	None	N
K/L	0.6442	likely_pathogenic	0.6714	pathogenic	0.402	Stabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
K/M	0.4015	ambiguous	0.4212	ambiguous	0.148	Stabilizing	1.0	D	0.668	neutral	None	None	None	None	N
K/N	0.5523	ambiguous	0.5672	pathogenic	-0.972	Destabilizing	1.0	D	0.755	deleterious	D	0.573673894	None	None	N
K/P	0.9299	likely_pathogenic	0.936	pathogenic	0.047	Stabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
K/Q	0.238	likely_benign	0.255	benign	-0.879	Destabilizing	1.0	D	0.752	deleterious	D	0.653722031	None	None	N
K/R	0.1017	likely_benign	0.108	benign	-0.92	Destabilizing	0.999	D	0.615	neutral	D	0.606297485	None	None	N
K/S	0.6357	likely_pathogenic	0.6637	pathogenic	-1.568	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
K/T	0.3885	ambiguous	0.4269	ambiguous	-1.166	Destabilizing	1.0	D	0.724	prob.delet.	D	0.599026593	None	None	N
K/V	0.7004	likely_pathogenic	0.7301	pathogenic	0.047	Stabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
K/W	0.8766	likely_pathogenic	0.8984	pathogenic	-0.143	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/Y	0.7657	likely_pathogenic	0.8014	pathogenic	0.171	Stabilizing	1.0	D	0.699	prob.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.