TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15140	45643;45644;45645	chr2:178621300;178621299;178621298	chr2:179486027;179486026;179486025
N2AB	13499	40720;40721;40722	chr2:178621300;178621299;178621298	chr2:179486027;179486026;179486025
N2A	12572	37939;37940;37941	chr2:178621300;178621299;178621298	chr2:179486027;179486026;179486025
N2B	6075	18448;18449;18450	chr2:178621300;178621299;178621298	chr2:179486027;179486026;179486025
Novex-1	6200	18823;18824;18825	chr2:178621300;178621299;178621298	chr2:179486027;179486026;179486025
Novex-2	6267	19024;19025;19026	chr2:178621300;178621299;178621298	chr2:179486027;179486026;179486025
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-103
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.3501
• 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
V/I	None	None	None	N	0.267	0.078	0.624871295421	gnomAD-4.0.0	1.59516E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86356E-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
V/A	0.1649	likely_benign	0.1667	benign	-1.712	Destabilizing	None	N	0.277	neutral	N	0.494860358	None	None	N
V/C	0.7317	likely_pathogenic	0.6845	pathogenic	-1.123	Destabilizing	0.356	N	0.547	neutral	None	None	None	None	N
V/D	0.4114	ambiguous	0.413	ambiguous	-1.645	Destabilizing	0.055	N	0.561	neutral	N	0.498571394	None	None	N
V/E	0.2731	likely_benign	0.2794	benign	-1.622	Destabilizing	0.072	N	0.509	neutral	None	None	None	None	N
V/F	0.1674	likely_benign	0.1734	benign	-1.275	Destabilizing	0.171	N	0.581	neutral	N	0.510373586	None	None	N
V/G	0.2621	likely_benign	0.2597	benign	-2.067	Highly Destabilizing	0.012	N	0.485	neutral	N	0.502141643	None	None	N
V/H	0.4899	ambiguous	0.4621	ambiguous	-1.605	Destabilizing	0.676	D	0.592	neutral	None	None	None	None	N
V/I	0.0739	likely_benign	0.0775	benign	-0.819	Destabilizing	None	N	0.267	neutral	N	0.510529285	None	None	N
V/K	0.3921	ambiguous	0.3955	ambiguous	-1.482	Destabilizing	0.038	N	0.518	neutral	None	None	None	None	N
V/L	0.1612	likely_benign	0.1768	benign	-0.819	Destabilizing	0.012	N	0.417	neutral	N	0.506989142	None	None	N
V/M	0.1346	likely_benign	0.1682	benign	-0.581	Destabilizing	0.214	N	0.566	neutral	None	None	None	None	N
V/N	0.2491	likely_benign	0.275	benign	-1.287	Destabilizing	0.038	N	0.597	neutral	None	None	None	None	N
V/P	0.8268	likely_pathogenic	0.8088	pathogenic	-1.083	Destabilizing	0.356	N	0.595	neutral	None	None	None	None	N
V/Q	0.2753	likely_benign	0.2902	benign	-1.436	Destabilizing	0.214	N	0.595	neutral	None	None	None	None	N
V/R	0.3397	likely_benign	0.3204	benign	-0.941	Destabilizing	0.214	N	0.605	neutral	None	None	None	None	N
V/S	0.1527	likely_benign	0.1585	benign	-1.831	Destabilizing	None	N	0.471	neutral	None	None	None	None	N
V/T	0.135	likely_benign	0.1434	benign	-1.697	Destabilizing	None	N	0.284	neutral	None	None	None	None	N
V/W	0.8372	likely_pathogenic	0.8214	pathogenic	-1.505	Destabilizing	0.864	D	0.623	neutral	None	None	None	None	N
V/Y	0.547	ambiguous	0.5338	ambiguous	-1.228	Destabilizing	0.356	N	0.569	neutral	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.