TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8125	24598;24599;24600	chr2:178718827;178718826;178718825	chr2:179583554;179583553;179583552
N2AB	7808	23647;23648;23649	chr2:178718827;178718826;178718825	chr2:179583554;179583553;179583552
N2A	6881	20866;20867;20868	chr2:178718827;178718826;178718825	chr2:179583554;179583553;179583552
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-66
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.424
• 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
N/S	None	None	None	N	0.091	0.144	0.134241683229	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
N/A	0.1422	likely_benign	0.1549	benign	-0.982	Destabilizing	None	N	0.242	neutral	None	None	None	None	I
N/C	0.2207	likely_benign	0.2549	benign	-0.012	Destabilizing	0.824	D	0.389	neutral	None	None	None	None	I
N/D	0.1016	likely_benign	0.1068	benign	-0.094	Destabilizing	0.062	N	0.24	neutral	D	0.531192675	None	None	I
N/E	0.2102	likely_benign	0.2378	benign	-0.034	Destabilizing	0.081	N	0.201	neutral	None	None	None	None	I
N/F	0.2883	likely_benign	0.3426	ambiguous	-0.841	Destabilizing	0.555	D	0.413	neutral	None	None	None	None	I
N/G	0.2074	likely_benign	0.2323	benign	-1.282	Destabilizing	0.035	N	0.251	neutral	None	None	None	None	I
N/H	0.0743	likely_benign	0.0797	benign	-0.959	Destabilizing	0.484	N	0.369	neutral	N	0.485652386	None	None	I
N/I	0.1346	likely_benign	0.154	benign	-0.234	Destabilizing	0.188	N	0.404	neutral	D	0.531886108	None	None	I
N/K	0.1527	likely_benign	0.1663	benign	-0.163	Destabilizing	0.062	N	0.191	neutral	N	0.453518538	None	None	I
N/L	0.1504	likely_benign	0.1693	benign	-0.234	Destabilizing	0.081	N	0.375	neutral	None	None	None	None	I
N/M	0.2011	likely_benign	0.2309	benign	0.236	Stabilizing	0.555	D	0.366	neutral	None	None	None	None	I
N/P	0.6848	likely_pathogenic	0.7367	pathogenic	-0.455	Destabilizing	0.38	N	0.377	neutral	None	None	None	None	I
N/Q	0.1753	likely_benign	0.1953	benign	-0.737	Destabilizing	0.38	N	0.324	neutral	None	None	None	None	I
N/R	0.1381	likely_benign	0.1545	benign	-0.112	Destabilizing	0.149	N	0.277	neutral	None	None	None	None	I
N/S	0.0693	likely_benign	0.073	benign	-0.76	Destabilizing	None	N	0.091	neutral	N	0.473144449	None	None	I
N/T	0.0841	likely_benign	0.0905	benign	-0.507	Destabilizing	None	N	0.095	neutral	N	0.483881518	None	None	I
N/V	0.1401	likely_benign	0.1587	benign	-0.455	Destabilizing	0.081	N	0.391	neutral	None	None	None	None	I
N/W	0.5115	ambiguous	0.5684	pathogenic	-0.553	Destabilizing	0.935	D	0.451	neutral	None	None	None	None	I
N/Y	0.1054	likely_benign	0.123	benign	-0.387	Destabilizing	0.484	N	0.387	neutral	N	0.492849261	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.