TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14355	43288;43289;43290	chr2:178633210;178633209;178633208	chr2:179497937;179497936;179497935
N2AB	12714	38365;38366;38367	chr2:178633210;178633209;178633208	chr2:179497937;179497936;179497935
N2A	11787	35584;35585;35586	chr2:178633210;178633209;178633208	chr2:179497937;179497936;179497935
N2B	5290	16093;16094;16095	chr2:178633210;178633209;178633208	chr2:179497937;179497936;179497935
Novex-1	5415	16468;16469;16470	chr2:178633210;178633209;178633208	chr2:179497937;179497936;179497935
Novex-2	5482	16669;16670;16671	chr2:178633210;178633209;178633208	chr2:179497937;179497936;179497935
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-94
• Domain position: 37
• Structural Position: 52
• Q(SASA): 0.2555
• 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
G/E	None	None	0.974	D	0.763	0.366	0.28722502521	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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
G/A	0.5274	ambiguous	0.4531	ambiguous	-0.437	Destabilizing	0.071	N	0.319	neutral	D	0.667199307	None	None	N
G/C	0.6966	likely_pathogenic	0.6492	pathogenic	-0.945	Destabilizing	0.997	D	0.764	deleterious	None	None	None	None	N
G/D	0.2015	likely_benign	0.1703	benign	-0.87	Destabilizing	0.99	D	0.738	deleterious	None	None	None	None	N
G/E	0.3797	ambiguous	0.3101	benign	-1.027	Destabilizing	0.974	D	0.763	deleterious	D	0.585329919	None	None	N
G/F	0.9409	likely_pathogenic	0.9129	pathogenic	-1.075	Destabilizing	0.997	D	0.823	deleterious	None	None	None	None	N
G/H	0.7959	likely_pathogenic	0.7354	pathogenic	-0.675	Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
G/I	0.8687	likely_pathogenic	0.8018	pathogenic	-0.517	Destabilizing	0.98	D	0.821	deleterious	None	None	None	None	N
G/K	0.8302	likely_pathogenic	0.7626	pathogenic	-1.079	Destabilizing	0.961	D	0.723	deleterious	None	None	None	None	N
G/L	0.8883	likely_pathogenic	0.8424	pathogenic	-0.517	Destabilizing	0.961	D	0.784	deleterious	None	None	None	None	N
G/M	0.9047	likely_pathogenic	0.8625	pathogenic	-0.525	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
G/N	0.3902	ambiguous	0.3231	benign	-0.688	Destabilizing	0.99	D	0.693	prob.delet.	None	None	None	None	N
G/P	0.9917	likely_pathogenic	0.9854	pathogenic	-0.456	Destabilizing	0.99	D	0.787	deleterious	None	None	None	None	N
G/Q	0.6906	likely_pathogenic	0.6135	pathogenic	-0.994	Destabilizing	0.99	D	0.801	deleterious	None	None	None	None	N
G/R	0.7474	likely_pathogenic	0.6811	pathogenic	-0.555	Destabilizing	0.429	N	0.384	neutral	D	0.667199307	None	None	N
G/S	0.2207	likely_benign	0.1934	benign	-0.82	Destabilizing	0.875	D	0.66	prob.neutral	None	None	None	None	N
G/T	0.6131	likely_pathogenic	0.5346	ambiguous	-0.913	Destabilizing	0.98	D	0.758	deleterious	None	None	None	None	N
G/V	0.7725	likely_pathogenic	0.6922	pathogenic	-0.456	Destabilizing	0.949	D	0.789	deleterious	D	0.670502407	None	None	N
G/W	0.8378	likely_pathogenic	0.7908	pathogenic	-1.23	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
G/Y	0.8378	likely_pathogenic	0.786	pathogenic	-0.904	Destabilizing	0.999	D	0.811	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.