TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22516	67771;67772;67773	chr2:178579651;178579650;178579649	chr2:179444378;179444377;179444376
N2AB	20875	62848;62849;62850	chr2:178579651;178579650;178579649	chr2:179444378;179444377;179444376
N2A	19948	60067;60068;60069	chr2:178579651;178579650;178579649	chr2:179444378;179444377;179444376
N2B	13451	40576;40577;40578	chr2:178579651;178579650;178579649	chr2:179444378;179444377;179444376
Novex-1	13576	40951;40952;40953	chr2:178579651;178579650;178579649	chr2:179444378;179444377;179444376
Novex-2	13643	41152;41153;41154	chr2:178579651;178579650;178579649	chr2:179444378;179444377;179444376
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-51
• Domain position: 66
• Structural Position: 100
• Q(SASA): 0.3682
• 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/R	rs1199563785	-0.851	0.989	N	0.831	0.425	0.656511762744	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
G/R	rs1199563785	-0.851	0.989	N	0.831	0.425	0.656511762744	gnomAD-4.0.0	1.59214E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86012E-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
G/A	0.4637	ambiguous	0.4459	ambiguous	-0.62	Destabilizing	0.928	D	0.721	prob.delet.	N	0.489052782	None	None	N
G/C	0.5391	ambiguous	0.4979	ambiguous	-0.907	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
G/D	0.2141	likely_benign	0.217	benign	-1.074	Destabilizing	0.05	N	0.485	neutral	None	None	None	None	N
G/E	0.3338	likely_benign	0.3444	ambiguous	-1.215	Destabilizing	0.957	D	0.751	deleterious	N	0.498927831	None	None	N
G/F	0.8422	likely_pathogenic	0.8354	pathogenic	-1.173	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
G/H	0.6335	likely_pathogenic	0.615	pathogenic	-0.982	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
G/I	0.8429	likely_pathogenic	0.8348	pathogenic	-0.576	Destabilizing	0.998	D	0.83	deleterious	None	None	None	None	N
G/K	0.6531	likely_pathogenic	0.6353	pathogenic	-1.252	Destabilizing	0.983	D	0.803	deleterious	None	None	None	None	N
G/L	0.7694	likely_pathogenic	0.7653	pathogenic	-0.576	Destabilizing	0.992	D	0.819	deleterious	None	None	None	None	N
G/M	0.7819	likely_pathogenic	0.7615	pathogenic	-0.464	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
G/N	0.2694	likely_benign	0.2523	benign	-0.819	Destabilizing	0.968	D	0.841	deleterious	None	None	None	None	N
G/P	0.9846	likely_pathogenic	0.9872	pathogenic	-0.555	Destabilizing	0.992	D	0.825	deleterious	None	None	None	None	N
G/Q	0.5117	ambiguous	0.5071	ambiguous	-1.127	Destabilizing	0.983	D	0.831	deleterious	None	None	None	None	N
G/R	0.5775	likely_pathogenic	0.5692	pathogenic	-0.739	Destabilizing	0.989	D	0.831	deleterious	N	0.516311297	None	None	N
G/S	0.2306	likely_benign	0.2194	benign	-0.969	Destabilizing	0.968	D	0.823	deleterious	None	None	None	None	N
G/T	0.5423	ambiguous	0.5014	ambiguous	-1.05	Destabilizing	0.983	D	0.797	deleterious	None	None	None	None	N
G/V	0.7345	likely_pathogenic	0.7298	pathogenic	-0.555	Destabilizing	0.989	D	0.819	deleterious	D	0.539948961	None	None	N
G/W	0.6269	likely_pathogenic	0.623	pathogenic	-1.369	Destabilizing	0.999	D	0.825	deleterious	N	0.481041066	None	None	N
G/Y	0.6758	likely_pathogenic	0.6489	pathogenic	-1.039	Destabilizing	0.999	D	0.825	deleterious	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.