TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16516	49771;49772;49773	chr2:178613263;178613262;178613261	chr2:179477990;179477989;179477988
N2AB	14875	44848;44849;44850	chr2:178613263;178613262;178613261	chr2:179477990;179477989;179477988
N2A	13948	42067;42068;42069	chr2:178613263;178613262;178613261	chr2:179477990;179477989;179477988
N2B	7451	22576;22577;22578	chr2:178613263;178613262;178613261	chr2:179477990;179477989;179477988
Novex-1	7576	22951;22952;22953	chr2:178613263;178613262;178613261	chr2:179477990;179477989;179477988
Novex-2	7643	23152;23153;23154	chr2:178613263;178613262;178613261	chr2:179477990;179477989;179477988
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-7
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.4959
• 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
T/I	rs1373830216	None	0.006	N	0.179	0.19	0.243972157842	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1373830216	None	0.006	N	0.179	0.19	0.243972157842	gnomAD-4.0.0	4.97044E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.78994E-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
T/A	0.0964	likely_benign	0.0775	benign	-0.799	Destabilizing	0.003	N	0.069	neutral	N	0.470240083	None	None	N
T/C	0.5796	likely_pathogenic	0.3793	ambiguous	-0.558	Destabilizing	0.944	D	0.368	neutral	None	None	None	None	N
T/D	0.6586	likely_pathogenic	0.5482	ambiguous	0.192	Stabilizing	0.388	N	0.378	neutral	None	None	None	None	N
T/E	0.5574	ambiguous	0.4204	ambiguous	0.216	Stabilizing	0.241	N	0.307	neutral	None	None	None	None	N
T/F	0.5214	ambiguous	0.3563	ambiguous	-0.927	Destabilizing	0.818	D	0.396	neutral	None	None	None	None	N
T/G	0.252	likely_benign	0.1979	benign	-1.058	Destabilizing	0.241	N	0.36	neutral	None	None	None	None	N
T/H	0.4515	ambiguous	0.3094	benign	-1.162	Destabilizing	0.944	D	0.373	neutral	None	None	None	None	N
T/I	0.2969	likely_benign	0.1608	benign	-0.198	Destabilizing	0.006	N	0.179	neutral	N	0.444622586	None	None	N
T/K	0.3955	ambiguous	0.3001	benign	-0.487	Destabilizing	0.241	N	0.307	neutral	None	None	None	None	N
T/L	0.1657	likely_benign	0.1057	benign	-0.198	Destabilizing	0.116	N	0.328	neutral	None	None	None	None	N
T/M	0.1617	likely_benign	0.1048	benign	-0.141	Destabilizing	0.818	D	0.371	neutral	None	None	None	None	N
T/N	0.2008	likely_benign	0.1441	benign	-0.55	Destabilizing	0.193	N	0.293	neutral	N	0.472857289	None	None	N
T/P	0.1408	likely_benign	0.1176	benign	-0.366	Destabilizing	0.001	N	0.117	neutral	N	0.465094088	None	None	N
T/Q	0.3114	likely_benign	0.2121	benign	-0.603	Destabilizing	0.69	D	0.396	neutral	None	None	None	None	N
T/R	0.4399	ambiguous	0.3392	benign	-0.308	Destabilizing	0.69	D	0.394	neutral	None	None	None	None	N
T/S	0.1173	likely_benign	0.1104	benign	-0.891	Destabilizing	0.001	N	0.136	neutral	N	0.461706975	None	None	N
T/V	0.2092	likely_benign	0.1184	benign	-0.366	Destabilizing	0.116	N	0.278	neutral	None	None	None	None	N
T/W	0.8121	likely_pathogenic	0.6852	pathogenic	-0.883	Destabilizing	0.981	D	0.421	neutral	None	None	None	None	N
T/Y	0.5859	likely_pathogenic	0.3931	ambiguous	-0.612	Destabilizing	0.818	D	0.387	neutral	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.