TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32434	97525;97526;97527	chr2:178542456;178542455;178542454	chr2:179407183;179407182;179407181
N2AB	30793	92602;92603;92604	chr2:178542456;178542455;178542454	chr2:179407183;179407182;179407181
N2A	29866	89821;89822;89823	chr2:178542456;178542455;178542454	chr2:179407183;179407182;179407181
N2B	23369	70330;70331;70332	chr2:178542456;178542455;178542454	chr2:179407183;179407182;179407181
Novex-1	23494	70705;70706;70707	chr2:178542456;178542455;178542454	chr2:179407183;179407182;179407181
Novex-2	23561	70906;70907;70908	chr2:178542456;178542455;178542454	chr2:179407183;179407182;179407181
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: Fn3-124
• Domain position: 36
• Structural Position: 37
• Q(SASA): 0.1737
• 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/A	rs756736710	-0.501	0.998	N	0.543	0.39	0.271763555656	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	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	0.3411	ambiguous	0.3238	benign	-0.69	Destabilizing	0.998	D	0.543	neutral	N	0.46842168	None	None	N
G/C	0.4469	ambiguous	0.3839	ambiguous	-1.25	Destabilizing	1.0	D	0.899	deleterious	N	0.479412818	None	None	N
G/D	0.9053	likely_pathogenic	0.8919	pathogenic	-0.872	Destabilizing	1.0	D	0.87	deleterious	N	0.47211821	None	None	N
G/E	0.9212	likely_pathogenic	0.9105	pathogenic	-0.918	Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
G/F	0.9429	likely_pathogenic	0.9317	pathogenic	-1.12	Destabilizing	1.0	D	0.937	deleterious	None	None	None	None	N
G/H	0.8644	likely_pathogenic	0.8443	pathogenic	-1.129	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
G/I	0.9227	likely_pathogenic	0.9098	pathogenic	-0.377	Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	N
G/K	0.967	likely_pathogenic	0.9612	pathogenic	-0.85	Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
G/L	0.9119	likely_pathogenic	0.8956	pathogenic	-0.377	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
G/M	0.9221	likely_pathogenic	0.9084	pathogenic	-0.56	Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
G/N	0.67	likely_pathogenic	0.6471	pathogenic	-0.673	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
G/P	0.9977	likely_pathogenic	0.9979	pathogenic	-0.443	Destabilizing	1.0	D	0.934	deleterious	None	None	None	None	N
G/Q	0.8677	likely_pathogenic	0.8477	pathogenic	-0.857	Destabilizing	1.0	D	0.932	deleterious	None	None	None	None	N
G/R	0.8978	likely_pathogenic	0.8725	pathogenic	-0.673	Destabilizing	1.0	D	0.936	deleterious	N	0.467016102	None	None	N
G/S	0.2142	likely_benign	0.1958	benign	-1.019	Destabilizing	0.991	D	0.585	neutral	N	0.486187451	None	None	N
G/T	0.6343	likely_pathogenic	0.6167	pathogenic	-0.975	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
G/V	0.8413	likely_pathogenic	0.8229	pathogenic	-0.443	Destabilizing	1.0	D	0.929	deleterious	N	0.51313934	None	None	N
G/W	0.9152	likely_pathogenic	0.8907	pathogenic	-1.379	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
G/Y	0.8938	likely_pathogenic	0.87	pathogenic	-0.942	Destabilizing	1.0	D	0.923	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.