TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10073	30442;30443;30444	chr2:178704153;178704152;178704151	chr2:179568880;179568879;179568878
N2AB	9756	29491;29492;29493	chr2:178704153;178704152;178704151	chr2:179568880;179568879;179568878
N2A	8829	26710;26711;26712	chr2:178704153;178704152;178704151	chr2:179568880;179568879;179568878
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: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-85
• Domain position: 85
• Structural Position: 176
• Q(SASA): 0.1763
• 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/V	None	None	0.219	None	0.167	0.105	0.128392430309	gnomAD-4.0.0	1.59158E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02352E-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
I/A	0.9453	likely_pathogenic	0.9563	pathogenic	-2.303	Highly Destabilizing	0.964	D	0.416	neutral	None	None	None	None	N
I/C	0.9878	likely_pathogenic	0.9883	pathogenic	-1.568	Destabilizing	1.0	D	0.483	neutral	None	None	None	None	N
I/D	0.9987	likely_pathogenic	0.9988	pathogenic	-2.301	Highly Destabilizing	0.999	D	0.592	neutral	None	None	None	None	N
I/E	0.9937	likely_pathogenic	0.9936	pathogenic	-2.23	Highly Destabilizing	0.999	D	0.594	neutral	None	None	None	None	N
I/F	0.8793	likely_pathogenic	0.8811	pathogenic	-1.48	Destabilizing	0.997	D	0.454	neutral	None	None	None	None	N
I/G	0.9939	likely_pathogenic	0.9946	pathogenic	-2.702	Highly Destabilizing	0.999	D	0.58	neutral	None	None	None	None	N
I/H	0.9974	likely_pathogenic	0.9973	pathogenic	-1.909	Destabilizing	1.0	D	0.604	neutral	None	None	None	None	N
I/K	0.9879	likely_pathogenic	0.9868	pathogenic	-1.719	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	N
I/L	0.5813	likely_pathogenic	0.5632	ambiguous	-1.219	Destabilizing	0.817	D	0.283	neutral	None	None	None	None	N
I/M	0.5089	ambiguous	0.5264	ambiguous	-1.07	Destabilizing	0.999	D	0.472	neutral	None	None	None	None	N
I/N	0.9814	likely_pathogenic	0.982	pathogenic	-1.66	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
I/P	0.9912	likely_pathogenic	0.9932	pathogenic	-1.555	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	N
I/Q	0.9928	likely_pathogenic	0.9931	pathogenic	-1.794	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
I/R	0.9833	likely_pathogenic	0.9822	pathogenic	-1.128	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
I/S	0.9701	likely_pathogenic	0.9745	pathogenic	-2.288	Highly Destabilizing	0.997	D	0.52	neutral	None	None	None	None	N
I/T	0.8648	likely_pathogenic	0.8942	pathogenic	-2.104	Highly Destabilizing	0.98	D	0.457	neutral	None	None	None	None	N
I/V	0.1769	likely_benign	0.1912	benign	-1.555	Destabilizing	0.219	N	0.167	neutral	None	None	None	None	N
I/W	0.9946	likely_pathogenic	0.9955	pathogenic	-1.641	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
I/Y	0.9875	likely_pathogenic	0.9881	pathogenic	-1.448	Destabilizing	0.999	D	0.477	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.