TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28450	85573;85574;85575	chr2:178560784;178560783;178560782	chr2:179425511;179425510;179425509
N2AB	26809	80650;80651;80652	chr2:178560784;178560783;178560782	chr2:179425511;179425510;179425509
N2A	25882	77869;77870;77871	chr2:178560784;178560783;178560782	chr2:179425511;179425510;179425509
N2B	19385	58378;58379;58380	chr2:178560784;178560783;178560782	chr2:179425511;179425510;179425509
Novex-1	19510	58753;58754;58755	chr2:178560784;178560783;178560782	chr2:179425511;179425510;179425509
Novex-2	19577	58954;58955;58956	chr2:178560784;178560783;178560782	chr2:179425511;179425510;179425509
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: Fn3-95
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4507
• 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	rs373453778	-0.068	0.058	N	0.319	0.151	0.107399877778	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
K/N	rs373453778	-0.068	0.058	N	0.319	0.151	0.107399877778	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/N	rs373453778	-0.068	0.058	N	0.319	0.151	0.107399877778	gnomAD-4.0.0	3.42125E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.4973E-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	0.5099	ambiguous	0.4868	ambiguous	-0.177	Destabilizing	0.016	N	0.476	neutral	None	None	None	None	I
K/C	0.6038	likely_pathogenic	0.5696	pathogenic	-0.309	Destabilizing	0.869	D	0.408	neutral	None	None	None	None	I
K/D	0.8925	likely_pathogenic	0.8951	pathogenic	0.216	Stabilizing	0.075	N	0.571	neutral	None	None	None	None	I
K/E	0.3693	ambiguous	0.3796	ambiguous	0.242	Stabilizing	0.012	N	0.447	neutral	N	0.474810327	None	None	I
K/F	0.8341	likely_pathogenic	0.8256	pathogenic	-0.258	Destabilizing	0.221	N	0.533	neutral	None	None	None	None	I
K/G	0.7068	likely_pathogenic	0.6643	pathogenic	-0.424	Destabilizing	0.075	N	0.502	neutral	None	None	None	None	I
K/H	0.4277	ambiguous	0.4107	ambiguous	-0.72	Destabilizing	0.366	N	0.446	neutral	None	None	None	None	I
K/I	0.2843	likely_benign	0.278	benign	0.403	Stabilizing	0.039	N	0.492	neutral	None	None	None	None	I
K/L	0.4578	ambiguous	0.4318	ambiguous	0.403	Stabilizing	0.016	N	0.46	neutral	None	None	None	None	I
K/M	0.2878	likely_benign	0.2794	benign	0.298	Stabilizing	0.303	N	0.45	neutral	N	0.486673612	None	None	I
K/N	0.6852	likely_pathogenic	0.6908	pathogenic	0.146	Stabilizing	0.058	N	0.319	neutral	N	0.486673612	None	None	I
K/P	0.7999	likely_pathogenic	0.7976	pathogenic	0.239	Stabilizing	0.366	N	0.528	neutral	None	None	None	None	I
K/Q	0.193	likely_benign	0.1807	benign	-0.069	Destabilizing	0.058	N	0.372	neutral	N	0.486673612	None	None	I
K/R	0.0718	likely_benign	0.0655	benign	-0.095	Destabilizing	None	N	0.095	neutral	N	0.397853604	None	None	I
K/S	0.613	likely_pathogenic	0.5895	pathogenic	-0.477	Destabilizing	0.075	N	0.37	neutral	None	None	None	None	I
K/T	0.2198	likely_benign	0.2236	benign	-0.284	Destabilizing	0.058	N	0.539	neutral	N	0.477277179	None	None	I
K/V	0.2724	likely_benign	0.2724	benign	0.239	Stabilizing	None	N	0.271	neutral	None	None	None	None	I
K/W	0.8467	likely_pathogenic	0.8231	pathogenic	-0.165	Destabilizing	0.869	D	0.513	neutral	None	None	None	None	I
K/Y	0.7114	likely_pathogenic	0.7023	pathogenic	0.165	Stabilizing	0.366	N	0.533	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.