TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8476	25651;25652;25653	chr2:178717308;178717307;178717306	chr2:179582035;179582034;179582033
N2AB	8159	24700;24701;24702	chr2:178717308;178717307;178717306	chr2:179582035;179582034;179582033
N2A	7232	21919;21920;21921	chr2:178717308;178717307;178717306	chr2:179582035;179582034;179582033
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-70
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.3924
• 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/T	None	None	0.478	N	0.455	0.479	0.393471546983	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	2.75482E-04	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	0.3165	likely_benign	0.263	benign	-0.436	Destabilizing	0.451	N	0.429	neutral	None	None	None	None	I
K/C	0.7024	likely_pathogenic	0.6509	pathogenic	-0.413	Destabilizing	0.994	D	0.619	neutral	None	None	None	None	I
K/D	0.5715	likely_pathogenic	0.4662	ambiguous	-0.025	Destabilizing	0.003	N	0.281	neutral	None	None	None	None	I
K/E	0.1496	likely_benign	0.1277	benign	0.066	Stabilizing	0.003	N	0.217	neutral	N	0.379444854	None	None	I
K/F	0.7523	likely_pathogenic	0.6967	pathogenic	-0.172	Destabilizing	0.945	D	0.607	neutral	None	None	None	None	I
K/G	0.5313	ambiguous	0.457	ambiguous	-0.789	Destabilizing	0.666	D	0.516	neutral	None	None	None	None	I
K/H	0.2427	likely_benign	0.2171	benign	-1.162	Destabilizing	0.947	D	0.557	neutral	None	None	None	None	I
K/I	0.289	likely_benign	0.2444	benign	0.466	Stabilizing	0.239	N	0.612	neutral	N	0.492733074	None	None	I
K/L	0.3125	likely_benign	0.283	benign	0.466	Stabilizing	0.106	N	0.573	neutral	None	None	None	None	I
K/M	0.2219	likely_benign	0.1925	benign	0.354	Stabilizing	0.951	D	0.543	neutral	None	None	None	None	I
K/N	0.3862	ambiguous	0.309	benign	-0.276	Destabilizing	0.429	N	0.39	neutral	N	0.476107396	None	None	I
K/P	0.8262	likely_pathogenic	0.7661	pathogenic	0.196	Stabilizing	0.934	D	0.549	neutral	None	None	None	None	I
K/Q	0.0971	likely_benign	0.0906	benign	-0.369	Destabilizing	0.154	N	0.439	neutral	N	0.444939127	None	None	I
K/R	0.0802	likely_benign	0.083	benign	-0.556	Destabilizing	0.217	N	0.4	neutral	N	0.462063451	None	None	I
K/S	0.3127	likely_benign	0.2544	benign	-0.913	Destabilizing	0.666	D	0.409	neutral	None	None	None	None	I
K/T	0.1157	likely_benign	0.0955	benign	-0.622	Destabilizing	0.478	N	0.455	neutral	N	0.446669924	None	None	I
K/V	0.2803	likely_benign	0.2363	benign	0.196	Stabilizing	0.135	N	0.594	neutral	None	None	None	None	I
K/W	0.7675	likely_pathogenic	0.7415	pathogenic	-0.06	Destabilizing	0.996	D	0.644	neutral	None	None	None	None	I
K/Y	0.5978	likely_pathogenic	0.5402	ambiguous	0.229	Stabilizing	0.668	D	0.6	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.