TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8114	24565;24566;24567	chr2:178718860;178718859;178718858	chr2:179583587;179583586;179583585
N2AB	7797	23614;23615;23616	chr2:178718860;178718859;178718858	chr2:179583587;179583586;179583585
N2A	6870	20833;20834;20835	chr2:178718860;178718859;178718858	chr2:179583587;179583586;179583585
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-66
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.326
• 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
G/D	rs923868923	None	0.275	N	0.423	0.247	0.104622674875	gnomAD-4.0.0	1.59143E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0248E-05

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
G/A	0.207	likely_benign	0.242	benign	-0.329	Destabilizing	0.996	D	0.512	neutral	N	0.477874974	None	None	N
G/C	0.4722	ambiguous	0.5106	ambiguous	-0.767	Destabilizing	1.0	D	0.701	prob.neutral	N	0.508602982	None	None	N
G/D	0.1718	likely_benign	0.1948	benign	None	Stabilizing	0.275	N	0.423	neutral	N	0.422130399	None	None	N
G/E	0.2825	likely_benign	0.3322	benign	-0.106	Destabilizing	0.996	D	0.607	neutral	None	None	None	None	N
G/F	0.7311	likely_pathogenic	0.7861	pathogenic	-0.786	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
G/H	0.578	likely_pathogenic	0.6302	pathogenic	-0.714	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
G/I	0.5601	ambiguous	0.6614	pathogenic	-0.188	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
G/K	0.6405	likely_pathogenic	0.7099	pathogenic	-0.698	Destabilizing	0.998	D	0.673	neutral	None	None	None	None	N
G/L	0.6368	likely_pathogenic	0.713	pathogenic	-0.188	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
G/M	0.6918	likely_pathogenic	0.7581	pathogenic	-0.31	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
G/N	0.2747	likely_benign	0.296	benign	-0.356	Destabilizing	0.998	D	0.635	neutral	None	None	None	None	N
G/P	0.9552	likely_pathogenic	0.9703	pathogenic	-0.196	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
G/Q	0.5094	ambiguous	0.5711	pathogenic	-0.528	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
G/R	0.5448	ambiguous	0.6183	pathogenic	-0.44	Destabilizing	0.999	D	0.709	prob.delet.	N	0.466772158	None	None	N
G/S	0.1564	likely_benign	0.174	benign	-0.67	Destabilizing	0.998	D	0.598	neutral	N	0.474899233	None	None	N
G/T	0.3916	ambiguous	0.4677	ambiguous	-0.68	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
G/V	0.365	ambiguous	0.4586	ambiguous	-0.196	Destabilizing	1.0	D	0.721	prob.delet.	N	0.485636881	None	None	N
G/W	0.6407	likely_pathogenic	0.6891	pathogenic	-1.033	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
G/Y	0.5205	ambiguous	0.5827	pathogenic	-0.623	Destabilizing	1.0	D	0.693	prob.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.