TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18830	56713;56714;56715	chr2:178599305;178599304;178599303	chr2:179464032;179464031;179464030
N2AB	17189	51790;51791;51792	chr2:178599305;178599304;178599303	chr2:179464032;179464031;179464030
N2A	16262	49009;49010;49011	chr2:178599305;178599304;178599303	chr2:179464032;179464031;179464030
N2B	9765	29518;29519;29520	chr2:178599305;178599304;178599303	chr2:179464032;179464031;179464030
Novex-1	9890	29893;29894;29895	chr2:178599305;178599304;178599303	chr2:179464032;179464031;179464030
Novex-2	9957	30094;30095;30096	chr2:178599305;178599304;178599303	chr2:179464032;179464031;179464030
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: Fn3-24
• Domain position: 47
• Structural Position: 63
• Q(SASA): 0.601
• 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	rs1004119141	None	0.942	N	0.371	0.204	0.188950314367	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	rs1004119141	None	0.942	N	0.371	0.204	0.188950314367	gnomAD-4.0.0	2.57737E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.80467E-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	0.5621	ambiguous	0.483	ambiguous	0.007	Stabilizing	0.754	D	0.445	neutral	None	None	None	None	N
K/C	0.8484	likely_pathogenic	0.7984	pathogenic	-0.471	Destabilizing	0.998	D	0.583	neutral	None	None	None	None	N
K/D	0.72	likely_pathogenic	0.6359	pathogenic	-0.252	Destabilizing	0.978	D	0.406	neutral	None	None	None	None	N
K/E	0.3795	ambiguous	0.299	benign	-0.266	Destabilizing	0.822	D	0.429	neutral	N	0.471743648	None	None	N
K/F	0.9117	likely_pathogenic	0.8671	pathogenic	-0.344	Destabilizing	0.956	D	0.535	neutral	None	None	None	None	N
K/G	0.5928	likely_pathogenic	0.5333	ambiguous	-0.113	Destabilizing	0.978	D	0.383	neutral	None	None	None	None	N
K/H	0.4883	ambiguous	0.4309	ambiguous	-0.181	Destabilizing	0.994	D	0.394	neutral	None	None	None	None	N
K/I	0.6172	likely_pathogenic	0.5109	ambiguous	0.239	Stabilizing	0.915	D	0.545	neutral	None	None	None	None	N
K/L	0.5369	ambiguous	0.4504	ambiguous	0.239	Stabilizing	0.514	D	0.435	neutral	None	None	None	None	N
K/M	0.4155	ambiguous	0.3277	benign	-0.126	Destabilizing	0.247	N	0.431	neutral	N	0.491390988	None	None	N
K/N	0.594	likely_pathogenic	0.5201	ambiguous	-0.004	Destabilizing	0.942	D	0.371	neutral	N	0.438036506	None	None	N
K/P	0.7008	likely_pathogenic	0.6472	pathogenic	0.184	Stabilizing	0.993	D	0.39	neutral	None	None	None	None	N
K/Q	0.2229	likely_benign	0.194	benign	-0.139	Destabilizing	0.942	D	0.377	neutral	N	0.480672562	None	None	N
K/R	0.1021	likely_benign	0.0999	benign	-0.102	Destabilizing	0.032	N	0.305	neutral	N	0.479539198	None	None	N
K/S	0.6295	likely_pathogenic	0.5658	pathogenic	-0.372	Destabilizing	0.86	D	0.389	neutral	None	None	None	None	N
K/T	0.3343	likely_benign	0.2774	benign	-0.272	Destabilizing	0.942	D	0.348	neutral	N	0.477690972	None	None	N
K/V	0.5447	ambiguous	0.4529	ambiguous	0.184	Stabilizing	0.754	D	0.389	neutral	None	None	None	None	N
K/W	0.8812	likely_pathogenic	0.8426	pathogenic	-0.452	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	N
K/Y	0.8127	likely_pathogenic	0.752	pathogenic	-0.099	Destabilizing	0.978	D	0.465	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.