TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2585	7978;7979;7980	chr2:178773211;178773210;178773209	chr2:179637938;179637937;179637936
N2AB	2585	7978;7979;7980	chr2:178773211;178773210;178773209	chr2:179637938;179637937;179637936
N2A	2585	7978;7979;7980	chr2:178773211;178773210;178773209	chr2:179637938;179637937;179637936
N2B	2539	7840;7841;7842	chr2:178773211;178773210;178773209	chr2:179637938;179637937;179637936
Novex-1	2539	7840;7841;7842	chr2:178773211;178773210;178773209	chr2:179637938;179637937;179637936
Novex-2	2539	7840;7841;7842	chr2:178773211;178773210;178773209	chr2:179637938;179637937;179637936
Novex-3	2585	7978;7979;7980	chr2:178773211;178773210;178773209	chr2:179637938;179637937;179637936

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-15
• Domain position: 53
• Structural Position: 134
• Q(SASA): 0.3313
• 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
K/N	rs2091789577	None	0.982	N	0.661	0.296	0.27479166964	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
K/N	rs2091789577	None	0.982	N	0.661	0.296	0.27479166964	gnomAD-4.0.0	6.57177E-06	None	None	None	None	N	None	0	6.54622E-05	None	0	0	None	0	0	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
K/A	0.5602	ambiguous	0.5274	ambiguous	-0.667	Destabilizing	0.91	D	0.543	neutral	None	None	None	None	N
K/C	0.7852	likely_pathogenic	0.7921	pathogenic	-0.747	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
K/D	0.5922	likely_pathogenic	0.5532	ambiguous	0.358	Stabilizing	0.986	D	0.636	neutral	None	None	None	None	N
K/E	0.3203	likely_benign	0.2823	benign	0.493	Stabilizing	0.939	D	0.554	neutral	D	0.537986701	None	None	N
K/F	0.8932	likely_pathogenic	0.8859	pathogenic	-0.309	Destabilizing	0.993	D	0.739	prob.delet.	None	None	None	None	N
K/G	0.5678	likely_pathogenic	0.5453	ambiguous	-1.033	Destabilizing	0.986	D	0.676	prob.neutral	None	None	None	None	N
K/H	0.4368	ambiguous	0.4492	ambiguous	-1.15	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
K/I	0.6013	likely_pathogenic	0.5765	pathogenic	0.287	Stabilizing	0.982	D	0.743	deleterious	D	0.58616413	None	None	N
K/L	0.5467	ambiguous	0.5282	ambiguous	0.287	Stabilizing	0.91	D	0.657	neutral	None	None	None	None	N
K/M	0.3089	likely_benign	0.2947	benign	0.062	Stabilizing	0.999	D	0.671	neutral	None	None	None	None	N
K/N	0.346	ambiguous	0.3122	benign	-0.351	Destabilizing	0.982	D	0.661	neutral	N	0.508840444	None	None	N
K/P	0.8034	likely_pathogenic	0.7902	pathogenic	-0.001	Destabilizing	0.993	D	0.705	prob.neutral	None	None	None	None	N
K/Q	0.2121	likely_benign	0.2066	benign	-0.381	Destabilizing	0.991	D	0.701	prob.neutral	N	0.504035804	None	None	N
K/R	0.1035	likely_benign	0.1061	benign	-0.364	Destabilizing	0.939	D	0.525	neutral	N	0.511894355	None	None	N
K/S	0.516	ambiguous	0.475	ambiguous	-1.163	Destabilizing	0.91	D	0.561	neutral	None	None	None	None	N
K/T	0.2217	likely_benign	0.2088	benign	-0.805	Destabilizing	0.17	N	0.375	neutral	N	0.512643924	None	None	N
K/V	0.5651	likely_pathogenic	0.5458	ambiguous	-0.001	Destabilizing	0.973	D	0.673	neutral	None	None	None	None	N
K/W	0.8874	likely_pathogenic	0.8887	pathogenic	-0.12	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
K/Y	0.7414	likely_pathogenic	0.7422	pathogenic	0.168	Stabilizing	0.998	D	0.726	prob.delet.	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.