TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28463	85612;85613;85614	chr2:178560745;178560744;178560743	chr2:179425472;179425471;179425470
N2AB	26822	80689;80690;80691	chr2:178560745;178560744;178560743	chr2:179425472;179425471;179425470
N2A	25895	77908;77909;77910	chr2:178560745;178560744;178560743	chr2:179425472;179425471;179425470
N2B	19398	58417;58418;58419	chr2:178560745;178560744;178560743	chr2:179425472;179425471;179425470
Novex-1	19523	58792;58793;58794	chr2:178560745;178560744;178560743	chr2:179425472;179425471;179425470
Novex-2	19590	58993;58994;58995	chr2:178560745;178560744;178560743	chr2:179425472;179425471;179425470
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-95
• Domain position: 14
• Structural Position: 15
• Q(SASA): 0.3904
• 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
L/F	None	None	0.988	N	0.663	0.257	0.625243557465	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
L/R	None	None	0.994	N	0.799	0.448	0.763205773721	gnomAD-4.0.0	1.59144E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85807E-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
L/A	0.3476	ambiguous	0.3934	ambiguous	-1.419	Destabilizing	0.938	D	0.499	neutral	None	None	None	None	N
L/C	0.4196	ambiguous	0.4718	ambiguous	-0.935	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
L/D	0.7852	likely_pathogenic	0.8283	pathogenic	-0.717	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	N
L/E	0.4734	ambiguous	0.5355	ambiguous	-0.76	Destabilizing	0.995	D	0.811	deleterious	None	None	None	None	N
L/F	0.1703	likely_benign	0.1885	benign	-1.25	Destabilizing	0.988	D	0.663	neutral	N	0.489468191	None	None	N
L/G	0.6358	likely_pathogenic	0.6931	pathogenic	-1.685	Destabilizing	0.995	D	0.809	deleterious	None	None	None	None	N
L/H	0.3461	ambiguous	0.4013	ambiguous	-0.998	Destabilizing	0.999	D	0.809	deleterious	N	0.471661954	None	None	N
L/I	0.0726	likely_benign	0.0758	benign	-0.792	Destabilizing	0.825	D	0.435	neutral	N	0.375486537	None	None	N
L/K	0.284	likely_benign	0.3352	benign	-0.809	Destabilizing	0.995	D	0.789	deleterious	None	None	None	None	N
L/M	0.128	likely_benign	0.1363	benign	-0.554	Destabilizing	0.995	D	0.685	prob.neutral	None	None	None	None	N
L/N	0.4954	ambiguous	0.5699	pathogenic	-0.553	Destabilizing	0.998	D	0.817	deleterious	None	None	None	None	N
L/P	0.3946	ambiguous	0.4138	ambiguous	-0.968	Destabilizing	0.998	D	0.822	deleterious	N	0.470901485	None	None	N
L/Q	0.2284	likely_benign	0.2743	benign	-0.792	Destabilizing	0.998	D	0.796	deleterious	None	None	None	None	N
L/R	0.2356	likely_benign	0.2778	benign	-0.245	Destabilizing	0.994	D	0.799	deleterious	N	0.462396233	None	None	N
L/S	0.4265	ambiguous	0.503	ambiguous	-1.163	Destabilizing	0.995	D	0.785	deleterious	None	None	None	None	N
L/T	0.2462	likely_benign	0.295	benign	-1.09	Destabilizing	0.991	D	0.68	prob.neutral	None	None	None	None	N
L/V	0.0793	likely_benign	0.0821	benign	-0.968	Destabilizing	0.067	N	0.165	neutral	N	0.33573607	None	None	N
L/W	0.3345	likely_benign	0.377	ambiguous	-1.261	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
L/Y	0.4173	ambiguous	0.4656	ambiguous	-1.013	Destabilizing	0.995	D	0.769	deleterious	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.