TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27603	83032;83033;83034	chr2:178563325;178563324;178563323	chr2:179428052;179428051;179428050
N2AB	25962	78109;78110;78111	chr2:178563325;178563324;178563323	chr2:179428052;179428051;179428050
N2A	25035	75328;75329;75330	chr2:178563325;178563324;178563323	chr2:179428052;179428051;179428050
N2B	18538	55837;55838;55839	chr2:178563325;178563324;178563323	chr2:179428052;179428051;179428050
Novex-1	18663	56212;56213;56214	chr2:178563325;178563324;178563323	chr2:179428052;179428051;179428050
Novex-2	18730	56413;56414;56415	chr2:178563325;178563324;178563323	chr2:179428052;179428051;179428050
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-89
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.3356
• Predicted PPI site: I

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	0.029	N	0.419	0.151	0.20549828249	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.2149	likely_benign	0.2321	benign	-0.064	Destabilizing	0.016	N	0.357	neutral	None	None	None	None	I
K/C	0.5247	ambiguous	0.5867	pathogenic	-0.304	Destabilizing	0.864	D	0.358	neutral	None	None	None	None	I
K/D	0.49	ambiguous	0.4928	ambiguous	0.24	Stabilizing	0.072	N	0.383	neutral	None	None	None	None	I
K/E	0.1455	likely_benign	0.1455	benign	0.265	Stabilizing	0.012	N	0.386	neutral	N	0.446445345	None	None	I
K/F	0.6359	likely_pathogenic	0.6583	pathogenic	-0.176	Destabilizing	0.214	N	0.391	neutral	None	None	None	None	I
K/G	0.3748	ambiguous	0.3963	ambiguous	-0.293	Destabilizing	0.038	N	0.369	neutral	None	None	None	None	I
K/H	0.2609	likely_benign	0.278	benign	-0.548	Destabilizing	0.356	N	0.377	neutral	None	None	None	None	I
K/I	0.2052	likely_benign	0.2122	benign	0.466	Stabilizing	0.029	N	0.419	neutral	N	0.385090242	None	None	I
K/L	0.2041	likely_benign	0.2093	benign	0.466	Stabilizing	None	N	0.249	neutral	None	None	None	None	I
K/M	0.1351	likely_benign	0.1433	benign	0.227	Stabilizing	0.214	N	0.378	neutral	None	None	None	None	I
K/N	0.3043	likely_benign	0.3225	benign	0.154	Stabilizing	0.055	N	0.352	neutral	N	0.466975333	None	None	I
K/P	0.8346	likely_pathogenic	0.8265	pathogenic	0.318	Stabilizing	0.356	N	0.431	neutral	None	None	None	None	I
K/Q	0.1076	likely_benign	0.114	benign	-0.002	Destabilizing	0.055	N	0.413	neutral	N	0.378105555	None	None	I
K/R	0.0841	likely_benign	0.0875	benign	-0.077	Destabilizing	None	N	0.077	neutral	N	0.445887985	None	None	I
K/S	0.2423	likely_benign	0.2821	benign	-0.407	Destabilizing	None	N	0.096	neutral	None	None	None	None	I
K/T	0.0848	likely_benign	0.0935	benign	-0.218	Destabilizing	0.001	N	0.192	neutral	N	0.348222578	None	None	I
K/V	0.1964	likely_benign	0.207	benign	0.318	Stabilizing	0.038	N	0.359	neutral	None	None	None	None	I
K/W	0.6685	likely_pathogenic	0.6892	pathogenic	-0.145	Destabilizing	0.864	D	0.435	neutral	None	None	None	None	I
K/Y	0.5201	ambiguous	0.5353	ambiguous	0.197	Stabilizing	0.356	N	0.371	neutral	None	None	None	None	I

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.