TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19173	57742;57743;57744	chr2:178597565;178597564;178597563	chr2:179462292;179462291;179462290
N2AB	17532	52819;52820;52821	chr2:178597565;178597564;178597563	chr2:179462292;179462291;179462290
N2A	16605	50038;50039;50040	chr2:178597565;178597564;178597563	chr2:179462292;179462291;179462290
N2B	10108	30547;30548;30549	chr2:178597565;178597564;178597563	chr2:179462292;179462291;179462290
Novex-1	10233	30922;30923;30924	chr2:178597565;178597564;178597563	chr2:179462292;179462291;179462290
Novex-2	10300	31123;31124;31125	chr2:178597565;178597564;178597563	chr2:179462292;179462291;179462290
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-117
• Domain position: 79
• Structural Position: 168
• Q(SASA): 0.6952
• 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	rs1009412718	0.251	0.942	N	0.669	0.294	0.308278614506	gnomAD-2.1.1	8.11E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
K/N	rs1009412718	0.251	0.942	N	0.669	0.294	0.308278614506	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs1009412718	0.251	0.942	N	0.669	0.294	0.308278614506	gnomAD-4.0.0	6.41728E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.24719E-04	9.58304E-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	0.4899	ambiguous	0.4906	ambiguous	-0.335	Destabilizing	0.86	D	0.585	neutral	None	None	None	None	N
K/C	0.6846	likely_pathogenic	0.6782	pathogenic	-0.505	Destabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
K/D	0.7877	likely_pathogenic	0.7887	pathogenic	0.404	Stabilizing	0.956	D	0.727	prob.delet.	None	None	None	None	N
K/E	0.2277	likely_benign	0.2262	benign	0.465	Stabilizing	0.698	D	0.529	neutral	N	0.484897451	None	None	N
K/F	0.8257	likely_pathogenic	0.8275	pathogenic	-0.302	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
K/G	0.614	likely_pathogenic	0.6185	pathogenic	-0.618	Destabilizing	0.956	D	0.644	neutral	None	None	None	None	N
K/H	0.3466	ambiguous	0.3345	benign	-0.928	Destabilizing	0.994	D	0.692	prob.neutral	None	None	None	None	N
K/I	0.4165	ambiguous	0.4261	ambiguous	0.358	Stabilizing	0.978	D	0.733	prob.delet.	None	None	None	None	N
K/L	0.4333	ambiguous	0.4458	ambiguous	0.358	Stabilizing	0.956	D	0.644	neutral	None	None	None	None	N
K/M	0.257	likely_benign	0.2648	benign	0.19	Stabilizing	0.997	D	0.685	prob.neutral	N	0.493836766	None	None	N
K/N	0.5558	ambiguous	0.558	ambiguous	-0.018	Destabilizing	0.942	D	0.669	neutral	N	0.518340808	None	None	N
K/P	0.9115	likely_pathogenic	0.9156	pathogenic	0.157	Stabilizing	0.978	D	0.736	prob.delet.	None	None	None	None	N
K/Q	0.1246	likely_benign	0.1229	benign	-0.164	Destabilizing	0.942	D	0.667	neutral	N	0.486671107	None	None	N
K/R	0.0808	likely_benign	0.0804	benign	-0.242	Destabilizing	0.014	N	0.249	neutral	N	0.455310837	None	None	N
K/S	0.4746	ambiguous	0.4827	ambiguous	-0.72	Destabilizing	0.86	D	0.585	neutral	None	None	None	None	N
K/T	0.1962	likely_benign	0.2025	benign	-0.471	Destabilizing	0.942	D	0.698	prob.neutral	N	0.450227517	None	None	N
K/V	0.381	ambiguous	0.3899	ambiguous	0.157	Stabilizing	0.956	D	0.724	prob.delet.	None	None	None	None	N
K/W	0.7441	likely_pathogenic	0.7428	pathogenic	-0.174	Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
K/Y	0.6676	likely_pathogenic	0.6691	pathogenic	0.148	Stabilizing	0.993	D	0.727	prob.delet.	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.