TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26373	79342;79343;79344	chr2:178567015;178567014;178567013	chr2:179431742;179431741;179431740
N2AB	24732	74419;74420;74421	chr2:178567015;178567014;178567013	chr2:179431742;179431741;179431740
N2A	23805	71638;71639;71640	chr2:178567015;178567014;178567013	chr2:179431742;179431741;179431740
N2B	17308	52147;52148;52149	chr2:178567015;178567014;178567013	chr2:179431742;179431741;179431740
Novex-1	17433	52522;52523;52524	chr2:178567015;178567014;178567013	chr2:179431742;179431741;179431740
Novex-2	17500	52723;52724;52725	chr2:178567015;178567014;178567013	chr2:179431742;179431741;179431740
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-79
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.0822
• 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
L/M	None	None	0.998	D	0.741	0.268	0.483596354421	gnomAD-4.0.0	4.77468E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71808E-06	0	3.0259E-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
L/A	0.4419	ambiguous	0.4502	ambiguous	-2.261	Highly Destabilizing	0.938	D	0.617	neutral	None	None	None	None	N
L/C	0.5977	likely_pathogenic	0.6089	pathogenic	-1.456	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
L/D	0.9874	likely_pathogenic	0.987	pathogenic	-2.258	Highly Destabilizing	0.991	D	0.839	deleterious	None	None	None	None	N
L/E	0.8418	likely_pathogenic	0.8512	pathogenic	-2.122	Highly Destabilizing	0.991	D	0.813	deleterious	None	None	None	None	N
L/F	0.702	likely_pathogenic	0.6842	pathogenic	-1.352	Destabilizing	0.994	D	0.738	prob.delet.	D	0.53774105	None	None	N
L/G	0.861	likely_pathogenic	0.8702	pathogenic	-2.721	Highly Destabilizing	0.991	D	0.807	deleterious	None	None	None	None	N
L/H	0.8325	likely_pathogenic	0.8444	pathogenic	-2.099	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/I	0.1648	likely_benign	0.1804	benign	-0.981	Destabilizing	0.968	D	0.608	neutral	None	None	None	None	N
L/K	0.7337	likely_pathogenic	0.7663	pathogenic	-1.749	Destabilizing	0.991	D	0.794	deleterious	None	None	None	None	N
L/M	0.2116	likely_benign	0.2209	benign	-0.852	Destabilizing	0.998	D	0.741	deleterious	D	0.53774105	None	None	N
L/N	0.9019	likely_pathogenic	0.9074	pathogenic	-1.808	Destabilizing	0.991	D	0.835	deleterious	None	None	None	None	N
L/P	0.9925	likely_pathogenic	0.9928	pathogenic	-1.384	Destabilizing	0.995	D	0.847	deleterious	None	None	None	None	N
L/Q	0.4874	ambiguous	0.5259	ambiguous	-1.815	Destabilizing	0.995	D	0.839	deleterious	None	None	None	None	N
L/R	0.5958	likely_pathogenic	0.6271	pathogenic	-1.307	Destabilizing	0.991	D	0.817	deleterious	None	None	None	None	N
L/S	0.6947	likely_pathogenic	0.7139	pathogenic	-2.465	Highly Destabilizing	0.976	D	0.734	prob.delet.	N	0.49865525	None	None	N
L/T	0.3764	ambiguous	0.4474	ambiguous	-2.206	Highly Destabilizing	0.18	N	0.456	neutral	None	None	None	None	N
L/V	0.1334	likely_benign	0.1453	benign	-1.384	Destabilizing	0.919	D	0.609	neutral	N	0.511740122	None	None	N
L/W	0.9008	likely_pathogenic	0.9021	pathogenic	-1.651	Destabilizing	0.999	D	0.831	deleterious	D	0.538501519	None	None	N
L/Y	0.9154	likely_pathogenic	0.9065	pathogenic	-1.384	Destabilizing	0.998	D	0.802	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.