TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2697	8314;8315;8316	chr2:178771238;178771237;178771236	chr2:179635965;179635964;179635963
N2AB	2697	8314;8315;8316	chr2:178771238;178771237;178771236	chr2:179635965;179635964;179635963
N2A	2697	8314;8315;8316	chr2:178771238;178771237;178771236	chr2:179635965;179635964;179635963
N2B	2651	8176;8177;8178	chr2:178771238;178771237;178771236	chr2:179635965;179635964;179635963
Novex-1	2651	8176;8177;8178	chr2:178771238;178771237;178771236	chr2:179635965;179635964;179635963
Novex-2	2651	8176;8177;8178	chr2:178771238;178771237;178771236	chr2:179635965;179635964;179635963
Novex-3	2697	8314;8315;8316	chr2:178771238;178771237;178771236	chr2:179635965;179635964;179635963

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-16
• Domain position: 77
• Structural Position: 163
• Q(SASA): 0.4691
• 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/I	None	None	0.82	D	0.741	0.316	0.470730462751	gnomAD-4.0.0	6.84104E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99313E-07	0	0
K/R	None	None	0.565	N	0.663	0.155	0.344251166708	gnomAD-4.0.0	6.84104E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99313E-07	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	0.312	likely_benign	0.3084	benign	-0.09	Destabilizing	0.633	D	0.703	prob.neutral	None	None	None	None	N
K/C	0.7333	likely_pathogenic	0.681	pathogenic	-0.293	Destabilizing	0.996	D	0.727	prob.delet.	None	None	None	None	N
K/D	0.6406	likely_pathogenic	0.6281	pathogenic	0.252	Stabilizing	0.923	D	0.725	prob.delet.	None	None	None	None	N
K/E	0.137	likely_benign	0.1329	benign	0.268	Stabilizing	0.565	D	0.691	prob.neutral	N	0.493325179	None	None	N
K/F	0.737	likely_pathogenic	0.7085	pathogenic	-0.277	Destabilizing	0.961	D	0.731	prob.delet.	None	None	None	None	N
K/G	0.5037	ambiguous	0.4961	ambiguous	-0.305	Destabilizing	0.775	D	0.719	prob.delet.	None	None	None	None	N
K/H	0.3472	ambiguous	0.3282	benign	-0.597	Destabilizing	0.989	D	0.707	prob.neutral	None	None	None	None	N
K/I	0.2883	likely_benign	0.2562	benign	0.397	Stabilizing	0.82	D	0.741	deleterious	D	0.566477477	None	None	N
K/L	0.355	ambiguous	0.342	ambiguous	0.397	Stabilizing	0.633	D	0.718	prob.delet.	None	None	None	None	N
K/M	0.1934	likely_benign	0.1748	benign	0.245	Stabilizing	0.989	D	0.707	prob.neutral	None	None	None	None	N
K/N	0.4243	ambiguous	0.4103	ambiguous	0.185	Stabilizing	0.901	D	0.69	prob.neutral	N	0.50859011	None	None	N
K/P	0.9139	likely_pathogenic	0.9005	pathogenic	0.264	Stabilizing	0.961	D	0.745	deleterious	None	None	None	None	N
K/Q	0.1118	likely_benign	0.1085	benign	None	Stabilizing	0.075	N	0.351	neutral	N	0.499831619	None	None	N
K/R	0.0908	likely_benign	0.0869	benign	-0.039	Destabilizing	0.565	D	0.663	neutral	N	0.509747634	None	None	N
K/S	0.3425	ambiguous	0.3334	benign	-0.389	Destabilizing	0.633	D	0.696	prob.neutral	None	None	None	None	N
K/T	0.1315	likely_benign	0.1234	benign	-0.214	Destabilizing	0.008	N	0.452	neutral	N	0.482003615	None	None	N
K/V	0.2497	likely_benign	0.2252	benign	0.264	Stabilizing	0.858	D	0.723	prob.delet.	None	None	None	None	N
K/W	0.7947	likely_pathogenic	0.7674	pathogenic	-0.24	Destabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	N
K/Y	0.6418	likely_pathogenic	0.6013	pathogenic	0.117	Stabilizing	0.987	D	0.747	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.