TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13797	41614;41615;41616	chr2:178636182;178636181;178636180	chr2:179500909;179500908;179500907
N2AB	12156	36691;36692;36693	chr2:178636182;178636181;178636180	chr2:179500909;179500908;179500907
N2A	11229	33910;33911;33912	chr2:178636182;178636181;178636180	chr2:179500909;179500908;179500907
N2B	4732	14419;14420;14421	chr2:178636182;178636181;178636180	chr2:179500909;179500908;179500907
Novex-1	4857	14794;14795;14796	chr2:178636182;178636181;178636180	chr2:179500909;179500908;179500907
Novex-2	4924	14995;14996;14997	chr2:178636182;178636181;178636180	chr2:179500909;179500908;179500907
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: Ig-88
• Domain position: 18
• Structural Position: 26
• Q(SASA): 0.3795
• 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/L	rs1205515315	-0.436	0.999	N	0.741	0.363	0.297375071883	gnomAD-4.0.0	2.74024E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60086E-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	0.2816	likely_benign	0.3436	ambiguous	-1.427	Destabilizing	0.998	D	0.693	prob.delet.	N	0.357346075	None	None	N
P/C	0.9179	likely_pathogenic	0.9525	pathogenic	-0.877	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
P/D	0.9115	likely_pathogenic	0.9441	pathogenic	-1.191	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
P/E	0.8367	likely_pathogenic	0.8971	pathogenic	-1.197	Destabilizing	0.999	D	0.69	prob.delet.	None	None	None	None	N
P/F	0.9281	likely_pathogenic	0.9626	pathogenic	-1.143	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
P/G	0.7907	likely_pathogenic	0.8503	pathogenic	-1.738	Destabilizing	1.0	D	0.666	prob.neutral	None	None	None	None	N
P/H	0.6962	likely_pathogenic	0.7982	pathogenic	-1.247	Destabilizing	0.844	D	0.418	neutral	None	None	None	None	N
P/I	0.8249	likely_pathogenic	0.8897	pathogenic	-0.678	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
P/K	0.8493	likely_pathogenic	0.9128	pathogenic	-1.129	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
P/L	0.4883	ambiguous	0.6175	pathogenic	-0.678	Destabilizing	0.999	D	0.741	deleterious	N	0.316959638	None	None	N
P/M	0.7892	likely_pathogenic	0.8625	pathogenic	-0.48	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
P/N	0.8317	likely_pathogenic	0.8931	pathogenic	-0.891	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
P/Q	0.6579	likely_pathogenic	0.761	pathogenic	-1.071	Destabilizing	0.999	D	0.768	deleterious	N	0.316590502	None	None	N
P/R	0.7067	likely_pathogenic	0.8129	pathogenic	-0.585	Destabilizing	0.999	D	0.753	deleterious	N	0.332477649	None	None	N
P/S	0.4996	ambiguous	0.6007	pathogenic	-1.408	Destabilizing	0.999	D	0.661	prob.neutral	N	0.345671811	None	None	N
P/T	0.4667	ambiguous	0.5786	pathogenic	-1.303	Destabilizing	1.0	D	0.801	deleterious	N	0.340485684	None	None	N
P/V	0.6788	likely_pathogenic	0.77	pathogenic	-0.892	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
P/W	0.9697	likely_pathogenic	0.9838	pathogenic	-1.32	Destabilizing	1.0	D	0.729	deleterious	None	None	None	None	N
P/Y	0.9016	likely_pathogenic	0.9435	pathogenic	-1.031	Destabilizing	0.999	D	0.809	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.