TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27547	82864;82865;82866	chr2:178563493;178563492;178563491	chr2:179428220;179428219;179428218
N2AB	25906	77941;77942;77943	chr2:178563493;178563492;178563491	chr2:179428220;179428219;179428218
N2A	24979	75160;75161;75162	chr2:178563493;178563492;178563491	chr2:179428220;179428219;179428218
N2B	18482	55669;55670;55671	chr2:178563493;178563492;178563491	chr2:179428220;179428219;179428218
Novex-1	18607	56044;56045;56046	chr2:178563493;178563492;178563491	chr2:179428220;179428219;179428218
Novex-2	18674	56245;56246;56247	chr2:178563493;178563492;178563491	chr2:179428220;179428219;179428218
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-88
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2919
• 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
E/K	rs779874042	-0.475	0.999	N	0.516	0.416	0.33440975612	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.63399E-04	None	0	0	0
E/K	rs779874042	-0.475	0.999	N	0.516	0.416	0.33440975612	gnomAD-4.0.0	1.02633E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.73901E-04	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
E/A	0.2318	likely_benign	0.2496	benign	-0.941	Destabilizing	0.999	D	0.663	neutral	N	0.472303383	None	None	N
E/C	0.7977	likely_pathogenic	0.8304	pathogenic	-0.503	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
E/D	0.6201	likely_pathogenic	0.6808	pathogenic	-1.292	Destabilizing	0.999	D	0.481	neutral	N	0.512843987	None	None	N
E/F	0.7911	likely_pathogenic	0.8254	pathogenic	-0.759	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
E/G	0.3548	ambiguous	0.374	ambiguous	-1.291	Destabilizing	1.0	D	0.753	deleterious	N	0.498854335	None	None	N
E/H	0.6258	likely_pathogenic	0.6887	pathogenic	-1.058	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
E/I	0.2827	likely_benign	0.3308	benign	0.013	Stabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
E/K	0.1411	likely_benign	0.165	benign	-0.656	Destabilizing	0.999	D	0.516	neutral	N	0.472823589	None	None	N
E/L	0.4453	ambiguous	0.4824	ambiguous	0.013	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
E/M	0.4072	ambiguous	0.442	ambiguous	0.553	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/N	0.6089	likely_pathogenic	0.6637	pathogenic	-1.033	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/P	0.9879	likely_pathogenic	0.992	pathogenic	-0.284	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Q	0.1174	likely_benign	0.1229	benign	-0.925	Destabilizing	1.0	D	0.604	neutral	N	0.479798574	None	None	N
E/R	0.2316	likely_benign	0.2674	benign	-0.53	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/S	0.3595	ambiguous	0.3945	ambiguous	-1.408	Destabilizing	0.999	D	0.544	neutral	None	None	None	None	N
E/T	0.31	likely_benign	0.3437	ambiguous	-1.107	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/V	0.1572	likely_benign	0.1765	benign	-0.284	Destabilizing	1.0	D	0.81	deleterious	N	0.458270131	None	None	N
E/W	0.923	likely_pathogenic	0.9457	pathogenic	-0.631	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
E/Y	0.7641	likely_pathogenic	0.8065	pathogenic	-0.513	Destabilizing	1.0	D	0.843	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.