TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5543	16852;16853;16854	chr2:178732342;178732341;178732340	chr2:179597069;179597068;179597067
N2AB	5226	15901;15902;15903	chr2:178732342;178732341;178732340	chr2:179597069;179597068;179597067
N2A	4299	13120;13121;13122	chr2:178732342;178732341;178732340	chr2:179597069;179597068;179597067
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-39
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.2312
• 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
A/T	rs1460498518	-1.394	0.98	N	0.507	0.266	0.173771789658	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14863E-04	0	None	0	0	None	0	None	0	0	0
A/T	rs1460498518	-1.394	0.98	N	0.507	0.266	0.173771789658	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
A/T	rs1460498518	-1.394	0.98	N	0.507	0.266	0.173771789658	gnomAD-4.0.0	6.57445E-06	None	None	None	None	N	None	2.41429E-05	0	None	0	0	None	0	0	0	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
A/C	0.8015	likely_pathogenic	0.8006	pathogenic	-1.528	Destabilizing	1.0	D	0.558	neutral	None	None	None	None	N
A/D	0.9666	likely_pathogenic	0.9712	pathogenic	-1.946	Destabilizing	0.994	D	0.557	neutral	N	0.480949416	None	None	N
A/E	0.949	likely_pathogenic	0.9523	pathogenic	-1.974	Destabilizing	0.985	D	0.518	neutral	None	None	None	None	N
A/F	0.9451	likely_pathogenic	0.944	pathogenic	-1.333	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
A/G	0.4414	ambiguous	0.4732	ambiguous	-1.214	Destabilizing	0.98	D	0.473	neutral	N	0.480949416	None	None	N
A/H	0.9826	likely_pathogenic	0.9841	pathogenic	-1.195	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	N
A/I	0.6657	likely_pathogenic	0.6598	pathogenic	-0.558	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	N
A/K	0.9843	likely_pathogenic	0.9853	pathogenic	-1.141	Destabilizing	0.985	D	0.52	neutral	None	None	None	None	N
A/L	0.6324	likely_pathogenic	0.6138	pathogenic	-0.558	Destabilizing	0.985	D	0.508	neutral	None	None	None	None	N
A/M	0.7843	likely_pathogenic	0.7848	pathogenic	-0.642	Destabilizing	1.0	D	0.573	neutral	None	None	None	None	N
A/N	0.939	likely_pathogenic	0.9455	pathogenic	-1.113	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
A/P	0.1987	likely_benign	0.1983	benign	-0.669	Destabilizing	0.011	N	0.342	neutral	N	0.261064087	None	None	N
A/Q	0.9511	likely_pathogenic	0.9532	pathogenic	-1.362	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	N
A/R	0.9644	likely_pathogenic	0.9658	pathogenic	-0.771	Destabilizing	0.999	D	0.576	neutral	None	None	None	None	N
A/S	0.2742	likely_benign	0.3007	benign	-1.419	Destabilizing	0.98	D	0.486	neutral	N	0.481296132	None	None	N
A/T	0.3578	ambiguous	0.3878	ambiguous	-1.363	Destabilizing	0.98	D	0.507	neutral	N	0.481989566	None	None	N
A/V	0.3001	likely_benign	0.3047	benign	-0.669	Destabilizing	0.98	D	0.503	neutral	N	0.46392388	None	None	N
A/W	0.9936	likely_pathogenic	0.9939	pathogenic	-1.592	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	N
A/Y	0.9781	likely_pathogenic	0.9789	pathogenic	-1.172	Destabilizing	0.999	D	0.625	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.