TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9547	28864;28865;28866	chr2:178709680;178709679;178709678	chr2:179574407;179574406;179574405
N2AB	9230	27913;27914;27915	chr2:178709680;178709679;178709678	chr2:179574407;179574406;179574405
N2A	8303	25132;25133;25134	chr2:178709680;178709679;178709678	chr2:179574407;179574406;179574405
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-81
• Domain position: 55
• Structural Position: 134
• Q(SASA): 0.3016
• 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
N/K	rs727505185	-0.031	0.992	None	0.604	0.26	0.168933306366	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.85E-06	0
N/K	rs727505185	-0.031	0.992	None	0.604	0.26	0.168933306366	gnomAD-4.0.0	1.59109E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85802E-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
N/A	0.5626	ambiguous	0.5211	ambiguous	-0.866	Destabilizing	0.988	D	0.645	neutral	None	None	None	None	N
N/C	0.6096	likely_pathogenic	0.6049	pathogenic	0.044	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
N/D	0.3474	ambiguous	0.3103	benign	-0.395	Destabilizing	0.992	D	0.555	neutral	None	None	None	None	N
N/E	0.8079	likely_pathogenic	0.7902	pathogenic	-0.279	Destabilizing	0.994	D	0.603	neutral	None	None	None	None	N
N/F	0.8967	likely_pathogenic	0.8904	pathogenic	-0.576	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
N/G	0.4453	ambiguous	0.391	ambiguous	-1.227	Destabilizing	0.994	D	0.555	neutral	None	None	None	None	N
N/H	0.2333	likely_benign	0.2198	benign	-0.933	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
N/I	0.7388	likely_pathogenic	0.7501	pathogenic	0.059	Stabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
N/K	0.7345	likely_pathogenic	0.7195	pathogenic	-0.228	Destabilizing	0.992	D	0.604	neutral	None	None	None	None	N
N/L	0.6625	likely_pathogenic	0.6711	pathogenic	0.059	Stabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
N/M	0.7549	likely_pathogenic	0.7462	pathogenic	0.443	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
N/P	0.904	likely_pathogenic	0.8835	pathogenic	-0.219	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
N/Q	0.629	likely_pathogenic	0.6169	pathogenic	-0.747	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
N/R	0.7048	likely_pathogenic	0.6942	pathogenic	-0.331	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
N/S	0.1186	likely_benign	0.1138	benign	-0.885	Destabilizing	0.825	D	0.287	neutral	None	None	None	None	N
N/T	0.3734	ambiguous	0.365	ambiguous	-0.565	Destabilizing	0.984	D	0.569	neutral	None	None	None	None	N
N/V	0.7343	likely_pathogenic	0.7409	pathogenic	-0.219	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
N/W	0.9627	likely_pathogenic	0.9603	pathogenic	-0.347	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
N/Y	0.4579	ambiguous	0.4494	ambiguous	-0.138	Destabilizing	1.0	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.