TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27103	81532;81533;81534	chr2:178564825;178564824;178564823	chr2:179429552;179429551;179429550
N2AB	25462	76609;76610;76611	chr2:178564825;178564824;178564823	chr2:179429552;179429551;179429550
N2A	24535	73828;73829;73830	chr2:178564825;178564824;178564823	chr2:179429552;179429551;179429550
N2B	18038	54337;54338;54339	chr2:178564825;178564824;178564823	chr2:179429552;179429551;179429550
Novex-1	18163	54712;54713;54714	chr2:178564825;178564824;178564823	chr2:179429552;179429551;179429550
Novex-2	18230	54913;54914;54915	chr2:178564825;178564824;178564823	chr2:179429552;179429551;179429550
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: Fn3-85
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7198
• 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/R	rs751284217	0.123	0.002	N	0.216	0.084	0.252681307341	gnomAD-2.1.1	7.2E-06	None	None	None	None	I	None	0	0	None	0	5.2E-05	None	0	None	0	7.9E-06	0
K/R	rs751284217	0.123	0.002	N	0.216	0.084	0.252681307341	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs751284217	0.123	0.002	N	0.216	0.084	0.252681307341	gnomAD-4.0.0	2.02995E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.40985E-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	0.174	likely_benign	0.1657	benign	-0.083	Destabilizing	0.004	N	0.132	neutral	None	None	None	None	I
K/C	0.5317	ambiguous	0.5124	ambiguous	-0.338	Destabilizing	0.983	D	0.445	neutral	None	None	None	None	I
K/D	0.3318	likely_benign	0.3158	benign	0.065	Stabilizing	0.264	N	0.466	neutral	None	None	None	None	I
K/E	0.1302	likely_benign	0.1227	benign	0.11	Stabilizing	0.007	N	0.186	neutral	N	0.459334498	None	None	I
K/F	0.705	likely_pathogenic	0.6938	pathogenic	-0.126	Destabilizing	0.836	D	0.477	neutral	None	None	None	None	I
K/G	0.2717	likely_benign	0.2664	benign	-0.328	Destabilizing	0.418	N	0.475	neutral	None	None	None	None	I
K/H	0.2399	likely_benign	0.2362	benign	-0.516	Destabilizing	0.836	D	0.454	neutral	None	None	None	None	I
K/I	0.3319	likely_benign	0.3204	benign	0.496	Stabilizing	0.213	N	0.493	neutral	N	0.484273015	None	None	I
K/L	0.2994	likely_benign	0.2865	benign	0.496	Stabilizing	0.129	N	0.475	neutral	None	None	None	None	I
K/M	0.2323	likely_benign	0.2246	benign	0.105	Stabilizing	0.836	D	0.454	neutral	None	None	None	None	I
K/N	0.2379	likely_benign	0.2252	benign	0.004	Stabilizing	0.351	N	0.373	neutral	N	0.5023387	None	None	I
K/P	0.2487	likely_benign	0.2207	benign	0.332	Stabilizing	0.001	N	0.125	neutral	None	None	None	None	I
K/Q	0.1061	likely_benign	0.1043	benign	-0.077	Destabilizing	0.351	N	0.389	neutral	N	0.501991984	None	None	I
K/R	0.0732	likely_benign	0.0752	benign	-0.134	Destabilizing	0.002	N	0.216	neutral	N	0.442349034	None	None	I
K/S	0.2355	likely_benign	0.2195	benign	-0.479	Destabilizing	0.129	N	0.322	neutral	None	None	None	None	I
K/T	0.1267	likely_benign	0.1213	benign	-0.265	Destabilizing	0.351	N	0.425	neutral	N	0.461414798	None	None	I
K/V	0.2522	likely_benign	0.2373	benign	0.332	Stabilizing	0.002	N	0.263	neutral	None	None	None	None	I
K/W	0.7172	likely_pathogenic	0.7167	pathogenic	-0.146	Destabilizing	0.983	D	0.488	neutral	None	None	None	None	I
K/Y	0.5527	ambiguous	0.5423	ambiguous	0.187	Stabilizing	0.94	D	0.475	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.