TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27853	83782;83783;83784	chr2:178562575;178562574;178562573	chr2:179427302;179427301;179427300
N2AB	26212	78859;78860;78861	chr2:178562575;178562574;178562573	chr2:179427302;179427301;179427300
N2A	25285	76078;76079;76080	chr2:178562575;178562574;178562573	chr2:179427302;179427301;179427300
N2B	18788	56587;56588;56589	chr2:178562575;178562574;178562573	chr2:179427302;179427301;179427300
Novex-1	18913	56962;56963;56964	chr2:178562575;178562574;178562573	chr2:179427302;179427301;179427300
Novex-2	18980	57163;57164;57165	chr2:178562575;178562574;178562573	chr2:179427302;179427301;179427300
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: Fn3-90
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.3725
• 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	None	None	0.123	N	0.455	0.252	0.270001397563	gnomAD-4.0.0	1.59873E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86699E-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
E/A	0.2307	likely_benign	0.1803	benign	-0.754	Destabilizing	0.03	N	0.474	neutral	N	0.47266855	None	None	N
E/C	0.8787	likely_pathogenic	0.8436	pathogenic	-0.445	Destabilizing	0.942	D	0.679	prob.neutral	None	None	None	None	N
E/D	0.2496	likely_benign	0.2172	benign	-1.027	Destabilizing	None	N	0.243	neutral	N	0.47094703	None	None	N
E/F	0.8208	likely_pathogenic	0.7707	pathogenic	0.018	Stabilizing	0.889	D	0.662	prob.neutral	None	None	None	None	N
E/G	0.3647	ambiguous	0.2959	benign	-1.138	Destabilizing	0.201	N	0.586	neutral	N	0.502764675	None	None	N
E/H	0.6669	likely_pathogenic	0.6013	pathogenic	-0.153	Destabilizing	0.653	D	0.479	neutral	None	None	None	None	N
E/I	0.4539	ambiguous	0.3709	ambiguous	0.299	Stabilizing	0.552	D	0.661	prob.neutral	None	None	None	None	N
E/K	0.3189	likely_benign	0.2568	benign	-0.511	Destabilizing	0.123	N	0.455	neutral	N	0.490394411	None	None	N
E/L	0.5322	ambiguous	0.453	ambiguous	0.299	Stabilizing	0.148	N	0.653	prob.neutral	None	None	None	None	N
E/M	0.5171	ambiguous	0.4411	ambiguous	0.648	Stabilizing	0.454	N	0.625	neutral	None	None	None	None	N
E/N	0.4581	ambiguous	0.379	ambiguous	-1.103	Destabilizing	0.074	N	0.411	neutral	None	None	None	None	N
E/P	0.8657	likely_pathogenic	0.7895	pathogenic	-0.031	Destabilizing	0.155	N	0.543	neutral	None	None	None	None	N
E/Q	0.2058	likely_benign	0.1839	benign	-0.938	Destabilizing	0.003	N	0.487	neutral	N	0.48135551	None	None	N
E/R	0.5089	ambiguous	0.4353	ambiguous	-0.145	Destabilizing	0.156	N	0.457	neutral	None	None	None	None	N
E/S	0.3071	likely_benign	0.241	benign	-1.402	Destabilizing	0.003	N	0.317	neutral	None	None	None	None	N
E/T	0.3067	likely_benign	0.2338	benign	-1.077	Destabilizing	0.121	N	0.469	neutral	None	None	None	None	N
E/V	0.2687	likely_benign	0.2215	benign	-0.031	Destabilizing	0.246	N	0.601	neutral	N	0.479545085	None	None	N
E/W	0.9609	likely_pathogenic	0.9497	pathogenic	0.323	Stabilizing	0.988	D	0.687	prob.delet.	None	None	None	None	N
E/Y	0.7822	likely_pathogenic	0.7314	pathogenic	0.288	Stabilizing	0.876	D	0.623	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.