TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23927	72004;72005;72006	chr2:178574353;178574352;178574351	chr2:179439080;179439079;179439078
N2AB	22286	67081;67082;67083	chr2:178574353;178574352;178574351	chr2:179439080;179439079;179439078
N2A	21359	64300;64301;64302	chr2:178574353;178574352;178574351	chr2:179439080;179439079;179439078
N2B	14862	44809;44810;44811	chr2:178574353;178574352;178574351	chr2:179439080;179439079;179439078
Novex-1	14987	45184;45185;45186	chr2:178574353;178574352;178574351	chr2:179439080;179439079;179439078
Novex-2	15054	45385;45386;45387	chr2:178574353;178574352;178574351	chr2:179439080;179439079;179439078
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-62
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2427
• 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
P/A	None	None	0.014	N	0.506	0.193	0.139678290688	gnomAD-4.0.0	4.10568E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39721E-06	0	0
P/Q	None	None	0.126	N	0.604	0.368	0.289098819767	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

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
P/A	0.0796	likely_benign	0.092	benign	-1.508	Destabilizing	0.014	N	0.506	neutral	N	0.489558617	None	None	N
P/C	0.4789	ambiguous	0.5557	ambiguous	-1.08	Destabilizing	0.998	D	0.829	deleterious	None	None	None	None	N
P/D	0.8501	likely_pathogenic	0.8791	pathogenic	-1.79	Destabilizing	0.956	D	0.788	deleterious	None	None	None	None	N
P/E	0.5201	ambiguous	0.5797	pathogenic	-1.839	Destabilizing	0.754	D	0.777	deleterious	None	None	None	None	N
P/F	0.646	likely_pathogenic	0.7348	pathogenic	-1.47	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
P/G	0.5127	ambiguous	0.5832	pathogenic	-1.762	Destabilizing	0.754	D	0.805	deleterious	None	None	None	None	N
P/H	0.3244	likely_benign	0.3875	ambiguous	-1.267	Destabilizing	0.994	D	0.813	deleterious	None	None	None	None	N
P/I	0.3748	ambiguous	0.448	ambiguous	-0.921	Destabilizing	0.956	D	0.851	deleterious	None	None	None	None	N
P/K	0.3913	ambiguous	0.4358	ambiguous	-1.172	Destabilizing	0.754	D	0.785	deleterious	None	None	None	None	N
P/L	0.2027	likely_benign	0.2629	benign	-0.921	Destabilizing	0.942	D	0.821	deleterious	N	0.514760226	None	None	N
P/M	0.4322	ambiguous	0.5065	ambiguous	-0.609	Destabilizing	0.994	D	0.814	deleterious	None	None	None	None	N
P/N	0.638	likely_pathogenic	0.7025	pathogenic	-0.981	Destabilizing	0.956	D	0.839	deleterious	None	None	None	None	N
P/Q	0.2487	likely_benign	0.3043	benign	-1.283	Destabilizing	0.126	N	0.604	neutral	N	0.510517037	None	None	N
P/R	0.233	likely_benign	0.2824	benign	-0.549	Destabilizing	0.89	D	0.841	deleterious	N	0.508884422	None	None	N
P/S	0.1761	likely_benign	0.2166	benign	-1.409	Destabilizing	0.698	D	0.775	deleterious	N	0.490678035	None	None	N
P/T	0.1787	likely_benign	0.2225	benign	-1.364	Destabilizing	0.942	D	0.797	deleterious	N	0.500428179	None	None	N
P/V	0.2623	likely_benign	0.3114	benign	-1.084	Destabilizing	0.915	D	0.817	deleterious	None	None	None	None	N
P/W	0.863	likely_pathogenic	0.9023	pathogenic	-1.593	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
P/Y	0.6459	likely_pathogenic	0.7303	pathogenic	-1.305	Destabilizing	0.978	D	0.841	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.