TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27157	81694;81695;81696	chr2:178564663;178564662;178564661	chr2:179429390;179429389;179429388
N2AB	25516	76771;76772;76773	chr2:178564663;178564662;178564661	chr2:179429390;179429389;179429388
N2A	24589	73990;73991;73992	chr2:178564663;178564662;178564661	chr2:179429390;179429389;179429388
N2B	18092	54499;54500;54501	chr2:178564663;178564662;178564661	chr2:179429390;179429389;179429388
Novex-1	18217	54874;54875;54876	chr2:178564663;178564662;178564661	chr2:179429390;179429389;179429388
Novex-2	18284	55075;55076;55077	chr2:178564663;178564662;178564661	chr2:179429390;179429389;179429388
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: Fn3-85
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.8815
• 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/N	None	None	0.007	N	0.246	0.077	0.0986583533028	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.595	likely_pathogenic	0.5428	ambiguous	-0.041	Destabilizing	0.543	D	0.493	neutral	None	None	None	None	I
K/C	0.8032	likely_pathogenic	0.7785	pathogenic	-0.298	Destabilizing	0.996	D	0.532	neutral	None	None	None	None	I
K/D	0.8582	likely_pathogenic	0.8198	pathogenic	-0.009	Destabilizing	0.59	D	0.498	neutral	None	None	None	None	I
K/E	0.4695	ambiguous	0.4085	ambiguous	-0.003	Destabilizing	0.028	N	0.152	neutral	N	0.436593711	None	None	I
K/F	0.8774	likely_pathogenic	0.843	pathogenic	-0.233	Destabilizing	0.984	D	0.505	neutral	None	None	None	None	I
K/G	0.7269	likely_pathogenic	0.6783	pathogenic	-0.243	Destabilizing	0.59	D	0.505	neutral	None	None	None	None	I
K/H	0.4799	ambiguous	0.4376	ambiguous	-0.493	Destabilizing	0.953	D	0.544	neutral	None	None	None	None	I
K/I	0.5472	ambiguous	0.4866	ambiguous	0.415	Stabilizing	0.953	D	0.511	neutral	None	None	None	None	I
K/L	0.5369	ambiguous	0.4844	ambiguous	0.415	Stabilizing	0.854	D	0.561	neutral	None	None	None	None	I
K/M	0.4552	ambiguous	0.4016	ambiguous	0.212	Stabilizing	0.994	D	0.537	neutral	N	0.496487705	None	None	I
K/N	0.7161	likely_pathogenic	0.6577	pathogenic	0.118	Stabilizing	0.007	N	0.246	neutral	N	0.52128982	None	None	I
K/P	0.5986	likely_pathogenic	0.5972	pathogenic	0.291	Stabilizing	0.004	N	0.163	neutral	None	None	None	None	I
K/Q	0.2558	likely_benign	0.226	benign	-0.071	Destabilizing	0.684	D	0.585	neutral	N	0.504165497	None	None	I
K/R	0.1016	likely_benign	0.0996	benign	-0.08	Destabilizing	0.684	D	0.538	neutral	N	0.493929861	None	None	I
K/S	0.7034	likely_pathogenic	0.6533	pathogenic	-0.376	Destabilizing	0.373	N	0.444	neutral	None	None	None	None	I
K/T	0.4624	ambiguous	0.4073	ambiguous	-0.22	Destabilizing	0.684	D	0.547	neutral	N	0.521385821	None	None	I
K/V	0.5323	ambiguous	0.4722	ambiguous	0.291	Stabilizing	0.854	D	0.547	neutral	None	None	None	None	I
K/W	0.8861	likely_pathogenic	0.8647	pathogenic	-0.227	Destabilizing	0.996	D	0.637	neutral	None	None	None	None	I
K/Y	0.7714	likely_pathogenic	0.7267	pathogenic	0.12	Stabilizing	0.984	D	0.505	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.