TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26398	79417;79418;79419	chr2:178566940;178566939;178566938	chr2:179431667;179431666;179431665
N2AB	24757	74494;74495;74496	chr2:178566940;178566939;178566938	chr2:179431667;179431666;179431665
N2A	23830	71713;71714;71715	chr2:178566940;178566939;178566938	chr2:179431667;179431666;179431665
N2B	17333	52222;52223;52224	chr2:178566940;178566939;178566938	chr2:179431667;179431666;179431665
Novex-1	17458	52597;52598;52599	chr2:178566940;178566939;178566938	chr2:179431667;179431666;179431665
Novex-2	17525	52798;52799;52800	chr2:178566940;178566939;178566938	chr2:179431667;179431666;179431665
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-80
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2653
• 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
I/T	rs749071678	-1.494	0.892	N	0.586	0.363	0.615014731015	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
I/T	rs749071678	-1.494	0.892	N	0.586	0.363	0.615014731015	gnomAD-4.0.0	6.84272E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15937E-05	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
I/A	0.4524	ambiguous	0.3463	ambiguous	-1.858	Destabilizing	0.845	D	0.476	neutral	None	None	None	None	N
I/C	0.8249	likely_pathogenic	0.7902	pathogenic	-1.506	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
I/D	0.9701	likely_pathogenic	0.9536	pathogenic	-1.562	Destabilizing	0.996	D	0.758	deleterious	None	None	None	None	N
I/E	0.9141	likely_pathogenic	0.8733	pathogenic	-1.554	Destabilizing	0.987	D	0.761	deleterious	None	None	None	None	N
I/F	0.4526	ambiguous	0.3909	ambiguous	-1.636	Destabilizing	0.967	D	0.573	neutral	N	0.490744168	None	None	N
I/G	0.9086	likely_pathogenic	0.8551	pathogenic	-2.18	Highly Destabilizing	0.987	D	0.758	deleterious	None	None	None	None	N
I/H	0.8811	likely_pathogenic	0.8346	pathogenic	-1.502	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
I/K	0.7416	likely_pathogenic	0.694	pathogenic	-1.171	Destabilizing	0.987	D	0.755	deleterious	None	None	None	None	N
I/L	0.2812	likely_benign	0.2468	benign	-1.033	Destabilizing	0.426	N	0.268	neutral	N	0.521521894	None	None	N
I/M	0.2053	likely_benign	0.1723	benign	-0.856	Destabilizing	0.983	D	0.561	neutral	N	0.493604551	None	None	N
I/N	0.7912	likely_pathogenic	0.7243	pathogenic	-1.065	Destabilizing	0.994	D	0.755	deleterious	N	0.497617022	None	None	N
I/P	0.8325	likely_pathogenic	0.8061	pathogenic	-1.279	Destabilizing	0.996	D	0.769	deleterious	None	None	None	None	N
I/Q	0.817	likely_pathogenic	0.7586	pathogenic	-1.284	Destabilizing	0.996	D	0.749	deleterious	None	None	None	None	N
I/R	0.6331	likely_pathogenic	0.58	pathogenic	-0.62	Destabilizing	0.987	D	0.755	deleterious	None	None	None	None	N
I/S	0.6148	likely_pathogenic	0.5266	ambiguous	-1.717	Destabilizing	0.983	D	0.698	prob.neutral	N	0.497242312	None	None	N
I/T	0.2122	likely_benign	0.1702	benign	-1.586	Destabilizing	0.892	D	0.586	neutral	N	0.510824898	None	None	N
I/V	0.0768	likely_benign	0.0668	benign	-1.279	Destabilizing	0.011	N	0.158	neutral	N	0.412255414	None	None	N
I/W	0.9475	likely_pathogenic	0.9369	pathogenic	-1.702	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
I/Y	0.8608	likely_pathogenic	0.8299	pathogenic	-1.429	Destabilizing	0.987	D	0.67	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.