TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23207	69844;69845;69846	chr2:178576625;178576624;178576623	chr2:179441352;179441351;179441350
N2AB	21566	64921;64922;64923	chr2:178576625;178576624;178576623	chr2:179441352;179441351;179441350
N2A	20639	62140;62141;62142	chr2:178576625;178576624;178576623	chr2:179441352;179441351;179441350
N2B	14142	42649;42650;42651	chr2:178576625;178576624;178576623	chr2:179441352;179441351;179441350
Novex-1	14267	43024;43025;43026	chr2:178576625;178576624;178576623	chr2:179441352;179441351;179441350
Novex-2	14334	43225;43226;43227	chr2:178576625;178576624;178576623	chr2:179441352;179441351;179441350
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-56
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.4502
• 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/E	None	None	0.568	N	0.549	0.343	0.434384183301	gnomAD-4.0.0	1.5916E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85914E-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	0.3603	ambiguous	0.3567	ambiguous	-0.531	Destabilizing	0.977	D	0.619	neutral	N	0.489381951	None	None	N
G/C	0.4438	ambiguous	0.4582	ambiguous	-0.919	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
G/D	0.2106	likely_benign	0.2249	benign	-0.892	Destabilizing	0.99	D	0.735	prob.delet.	None	None	None	None	N
G/E	0.3624	ambiguous	0.3945	ambiguous	-1.034	Destabilizing	0.568	D	0.549	neutral	N	0.480494407	None	None	N
G/F	0.7677	likely_pathogenic	0.7599	pathogenic	-1.109	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
G/H	0.5446	ambiguous	0.5484	ambiguous	-0.843	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
G/I	0.7336	likely_pathogenic	0.7479	pathogenic	-0.501	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
G/K	0.6463	likely_pathogenic	0.6645	pathogenic	-1.095	Destabilizing	0.289	N	0.555	neutral	None	None	None	None	N
G/L	0.7315	likely_pathogenic	0.7243	pathogenic	-0.501	Destabilizing	0.995	D	0.796	deleterious	None	None	None	None	N
G/M	0.7246	likely_pathogenic	0.7132	pathogenic	-0.416	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
G/N	0.2286	likely_benign	0.221	benign	-0.704	Destabilizing	0.995	D	0.827	deleterious	None	None	None	None	N
G/P	0.9805	likely_pathogenic	0.9777	pathogenic	-0.474	Destabilizing	0.998	D	0.847	deleterious	None	None	None	None	N
G/Q	0.5268	ambiguous	0.5475	ambiguous	-1.007	Destabilizing	0.995	D	0.836	deleterious	None	None	None	None	N
G/R	0.5711	likely_pathogenic	0.5962	pathogenic	-0.603	Destabilizing	0.987	D	0.819	deleterious	N	0.512361278	None	None	N
G/S	0.194	likely_benign	0.1879	benign	-0.885	Destabilizing	0.983	D	0.768	deleterious	None	None	None	None	N
G/T	0.3939	ambiguous	0.3787	ambiguous	-0.961	Destabilizing	0.995	D	0.819	deleterious	None	None	None	None	N
G/V	0.6159	likely_pathogenic	0.6263	pathogenic	-0.474	Destabilizing	0.997	D	0.807	deleterious	D	0.527111398	None	None	N
G/W	0.6457	likely_pathogenic	0.6576	pathogenic	-1.294	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
G/Y	0.5823	likely_pathogenic	0.5743	pathogenic	-0.949	Destabilizing	1.0	D	0.861	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.