TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15747	47464;47465;47466	chr2:178618219;178618218;178618217	chr2:179482946;179482945;179482944
N2AB	14106	42541;42542;42543	chr2:178618219;178618218;178618217	chr2:179482946;179482945;179482944
N2A	13179	39760;39761;39762	chr2:178618219;178618218;178618217	chr2:179482946;179482945;179482944
N2B	6682	20269;20270;20271	chr2:178618219;178618218;178618217	chr2:179482946;179482945;179482944
Novex-1	6807	20644;20645;20646	chr2:178618219;178618218;178618217	chr2:179482946;179482945;179482944
Novex-2	6874	20845;20846;20847	chr2:178618219;178618218;178618217	chr2:179482946;179482945;179482944
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-1
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.6739
• 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
D/G	None	None	0.376	N	0.481	0.165	0.230578612272	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
D/A	0.1042	likely_benign	0.0895	benign	0.096	Stabilizing	0.004	N	0.461	neutral	N	0.496833439	None	None	N
D/C	0.5169	ambiguous	0.401	ambiguous	-0.025	Destabilizing	0.977	D	0.756	deleterious	None	None	None	None	N
D/E	0.1003	likely_benign	0.0802	benign	-0.348	Destabilizing	0.004	N	0.278	neutral	N	0.462688768	None	None	N
D/F	0.5387	ambiguous	0.4694	ambiguous	-0.131	Destabilizing	0.919	D	0.751	deleterious	None	None	None	None	N
D/G	0.1096	likely_benign	0.0941	benign	0.019	Stabilizing	0.376	N	0.481	neutral	N	0.48569223	None	None	N
D/H	0.2415	likely_benign	0.2141	benign	0.45	Stabilizing	0.97	D	0.518	neutral	D	0.609275636	None	None	N
D/I	0.2714	likely_benign	0.2282	benign	0.226	Stabilizing	0.848	D	0.783	deleterious	None	None	None	None	N
D/K	0.1753	likely_benign	0.1416	benign	0.449	Stabilizing	0.444	N	0.549	neutral	None	None	None	None	N
D/L	0.2615	likely_benign	0.2182	benign	0.226	Stabilizing	0.737	D	0.628	neutral	None	None	None	None	N
D/M	0.4621	ambiguous	0.3819	ambiguous	0.07	Stabilizing	0.992	D	0.731	deleterious	None	None	None	None	N
D/N	0.088	likely_benign	0.0799	benign	0.377	Stabilizing	0.009	N	0.306	neutral	D	0.566821943	None	None	N
D/P	0.3427	ambiguous	0.2811	benign	0.2	Stabilizing	0.919	D	0.55	neutral	None	None	None	None	N
D/Q	0.187	likely_benign	0.1517	benign	0.341	Stabilizing	0.737	D	0.457	neutral	None	None	None	None	N
D/R	0.2183	likely_benign	0.1859	benign	0.601	Stabilizing	0.848	D	0.706	prob.delet.	None	None	None	None	N
D/S	0.0875	likely_benign	0.0762	benign	0.257	Stabilizing	0.444	N	0.424	neutral	None	None	None	None	N
D/T	0.1548	likely_benign	0.1244	benign	0.318	Stabilizing	0.047	N	0.374	neutral	None	None	None	None	N
D/V	0.1585	likely_benign	0.1388	benign	0.2	Stabilizing	0.376	N	0.631	neutral	N	0.495920606	None	None	N
D/W	0.7872	likely_pathogenic	0.7187	pathogenic	-0.146	Destabilizing	0.992	D	0.793	deleterious	None	None	None	None	N
D/Y	0.2434	likely_benign	0.2157	benign	0.083	Stabilizing	0.963	D	0.751	deleterious	D	0.569033364	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.