TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8994	27205;27206;27207	chr2:178713154;178713153;178713152	chr2:179577881;179577880;179577879
N2AB	8677	26254;26255;26256	chr2:178713154;178713153;178713152	chr2:179577881;179577880;179577879
N2A	7750	23473;23474;23475	chr2:178713154;178713153;178713152	chr2:179577881;179577880;179577879
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-75
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.1837
• 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/V	None	None	0.999	D	0.833	0.631	0.893417946627	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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	0.2711	likely_benign	0.3226	benign	-0.823	Destabilizing	0.995	D	0.802	deleterious	D	0.560075359	None	None	N
G/C	0.5334	ambiguous	0.6679	pathogenic	-0.846	Destabilizing	1.0	D	0.817	deleterious	D	0.658552455	None	None	N
G/D	0.6021	likely_pathogenic	0.7272	pathogenic	-1.819	Destabilizing	0.999	D	0.845	deleterious	D	0.609858599	None	None	N
G/E	0.713	likely_pathogenic	0.8371	pathogenic	-1.824	Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
G/F	0.9155	likely_pathogenic	0.9565	pathogenic	-1.115	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
G/H	0.819	likely_pathogenic	0.8989	pathogenic	-1.673	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
G/I	0.8768	likely_pathogenic	0.9434	pathogenic	-0.256	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/K	0.76	likely_pathogenic	0.8715	pathogenic	-1.301	Destabilizing	0.998	D	0.867	deleterious	None	None	None	None	N
G/L	0.8503	likely_pathogenic	0.9198	pathogenic	-0.256	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
G/M	0.8774	likely_pathogenic	0.9374	pathogenic	-0.085	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/N	0.7418	likely_pathogenic	0.8414	pathogenic	-1.085	Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
G/P	0.9884	likely_pathogenic	0.9925	pathogenic	-0.404	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
G/Q	0.7172	likely_pathogenic	0.8295	pathogenic	-1.211	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
G/R	0.579	likely_pathogenic	0.7287	pathogenic	-1.055	Destabilizing	0.777	D	0.782	deleterious	D	0.658350651	None	None	N
G/S	0.224	likely_benign	0.2962	benign	-1.308	Destabilizing	0.999	D	0.866	deleterious	D	0.63240893	None	None	N
G/T	0.6311	likely_pathogenic	0.7492	pathogenic	-1.239	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
G/V	0.7485	likely_pathogenic	0.8617	pathogenic	-0.404	Destabilizing	0.999	D	0.833	deleterious	D	0.642533094	None	None	N
G/W	0.8524	likely_pathogenic	0.9112	pathogenic	-1.647	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
G/Y	0.8949	likely_pathogenic	0.9456	pathogenic	-1.181	Destabilizing	1.0	D	0.857	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.