TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25608	77047;77048;77049	chr2:178569310;178569309;178569308	chr2:179434037;179434036;179434035
N2AB	23967	72124;72125;72126	chr2:178569310;178569309;178569308	chr2:179434037;179434036;179434035
N2A	23040	69343;69344;69345	chr2:178569310;178569309;178569308	chr2:179434037;179434036;179434035
N2B	16543	49852;49853;49854	chr2:178569310;178569309;178569308	chr2:179434037;179434036;179434035
Novex-1	16668	50227;50228;50229	chr2:178569310;178569309;178569308	chr2:179434037;179434036;179434035
Novex-2	16735	50428;50429;50430	chr2:178569310;178569309;178569308	chr2:179434037;179434036;179434035
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-74
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.2021
• 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/P	None	None	0.998	N	0.839	0.568	0.862729480221	gnomAD-4.0.0	1.59571E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86584E-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	0.8858	likely_pathogenic	0.901	pathogenic	-2.321	Highly Destabilizing	0.936	D	0.693	prob.neutral	None	None	None	None	N
L/C	0.7423	likely_pathogenic	0.7651	pathogenic	-1.574	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
L/D	0.9983	likely_pathogenic	0.9981	pathogenic	-2.296	Highly Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
L/E	0.9898	likely_pathogenic	0.9895	pathogenic	-2.179	Highly Destabilizing	0.994	D	0.834	deleterious	None	None	None	None	N
L/F	0.2566	likely_benign	0.3329	benign	-1.489	Destabilizing	0.035	N	0.35	neutral	None	None	None	None	N
L/G	0.9764	likely_pathogenic	0.9792	pathogenic	-2.78	Highly Destabilizing	0.995	D	0.805	deleterious	None	None	None	None	N
L/H	0.9594	likely_pathogenic	0.9599	pathogenic	-2.162	Highly Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
L/I	0.1001	likely_benign	0.1028	benign	-1.048	Destabilizing	0.058	N	0.718	prob.delet.	None	None	None	None	N
L/K	0.9829	likely_pathogenic	0.982	pathogenic	-1.771	Destabilizing	0.86	D	0.817	deleterious	None	None	None	None	N
L/M	0.1866	likely_benign	0.204	benign	-0.873	Destabilizing	0.903	D	0.712	prob.delet.	N	0.511884433	None	None	N
L/N	0.986	likely_pathogenic	0.9853	pathogenic	-1.794	Destabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
L/P	0.9116	likely_pathogenic	0.9076	pathogenic	-1.447	Destabilizing	0.998	D	0.839	deleterious	N	0.504560647	None	None	N
L/Q	0.9483	likely_pathogenic	0.9496	pathogenic	-1.83	Destabilizing	0.995	D	0.813	deleterious	D	0.532648487	None	None	N
L/R	0.9675	likely_pathogenic	0.9678	pathogenic	-1.306	Destabilizing	0.984	D	0.817	deleterious	D	0.550752742	None	None	N
L/S	0.9742	likely_pathogenic	0.9757	pathogenic	-2.464	Highly Destabilizing	0.99	D	0.795	deleterious	None	None	None	None	N
L/T	0.8373	likely_pathogenic	0.8456	pathogenic	-2.217	Highly Destabilizing	0.898	D	0.785	deleterious	None	None	None	None	N
L/V	0.1138	likely_benign	0.1227	benign	-1.447	Destabilizing	0.003	N	0.395	neutral	N	0.483334439	None	None	N
L/W	0.8134	likely_pathogenic	0.8298	pathogenic	-1.759	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
L/Y	0.8665	likely_pathogenic	0.8848	pathogenic	-1.508	Destabilizing	0.707	D	0.797	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.