TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20940	63043;63044;63045	chr2:178588907;178588906;178588905	chr2:179453634;179453633;179453632
N2AB	19299	58120;58121;58122	chr2:178588907;178588906;178588905	chr2:179453634;179453633;179453632
N2A	18372	55339;55340;55341	chr2:178588907;178588906;178588905	chr2:179453634;179453633;179453632
N2B	11875	35848;35849;35850	chr2:178588907;178588906;178588905	chr2:179453634;179453633;179453632
Novex-1	12000	36223;36224;36225	chr2:178588907;178588906;178588905	chr2:179453634;179453633;179453632
Novex-2	12067	36424;36425;36426	chr2:178588907;178588906;178588905	chr2:179453634;179453633;179453632
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-39
• Domain position: 77
• Structural Position: 110
• Q(SASA): 0.0952
• 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	None	None	0.999	D	0.723	0.534	0.517765160837	gnomAD-4.0.0	1.59298E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86022E-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
A/C	0.8973	likely_pathogenic	0.9029	pathogenic	-1.866	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/D	0.9988	likely_pathogenic	0.9987	pathogenic	-2.955	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
A/E	0.9979	likely_pathogenic	0.9975	pathogenic	-2.739	Highly Destabilizing	0.999	D	0.781	deleterious	D	0.561280263	None	None	N
A/F	0.9951	likely_pathogenic	0.9953	pathogenic	-0.667	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
A/G	0.3029	likely_benign	0.4107	ambiguous	-2.133	Highly Destabilizing	0.998	D	0.589	neutral	D	0.524057795	None	None	N
A/H	0.999	likely_pathogenic	0.9987	pathogenic	-1.98	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
A/I	0.9879	likely_pathogenic	0.9888	pathogenic	-0.573	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
A/K	0.9995	likely_pathogenic	0.9994	pathogenic	-1.436	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
A/L	0.9445	likely_pathogenic	0.9534	pathogenic	-0.573	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
A/M	0.9793	likely_pathogenic	0.9816	pathogenic	-1.137	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/N	0.9966	likely_pathogenic	0.9963	pathogenic	-1.907	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
A/P	0.9038	likely_pathogenic	0.918	pathogenic	-0.924	Destabilizing	0.64	D	0.531	neutral	D	0.543429497	None	None	N
A/Q	0.9955	likely_pathogenic	0.9948	pathogenic	-1.659	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
A/R	0.9973	likely_pathogenic	0.9966	pathogenic	-1.486	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
A/S	0.5533	ambiguous	0.5105	ambiguous	-2.24	Highly Destabilizing	0.998	D	0.602	neutral	N	0.502773534	None	None	N
A/T	0.9244	likely_pathogenic	0.9216	pathogenic	-1.921	Destabilizing	0.999	D	0.723	prob.delet.	D	0.54595703	None	None	N
A/V	0.9277	likely_pathogenic	0.935	pathogenic	-0.924	Destabilizing	0.998	D	0.687	prob.neutral	D	0.536375152	None	None	N
A/W	0.9994	likely_pathogenic	0.9993	pathogenic	-1.283	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
A/Y	0.998	likely_pathogenic	0.9979	pathogenic	-0.997	Destabilizing	1.0	D	0.889	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.