TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2910	8953;8954;8955	chr2:178769853;178769852;178769851	chr2:179634580;179634579;179634578
N2AB	2910	8953;8954;8955	chr2:178769853;178769852;178769851	chr2:179634580;179634579;179634578
N2A	2910	8953;8954;8955	chr2:178769853;178769852;178769851	chr2:179634580;179634579;179634578
N2B	2864	8815;8816;8817	chr2:178769853;178769852;178769851	chr2:179634580;179634579;179634578
Novex-1	2864	8815;8816;8817	chr2:178769853;178769852;178769851	chr2:179634580;179634579;179634578
Novex-2	2864	8815;8816;8817	chr2:178769853;178769852;178769851	chr2:179634580;179634579;179634578
Novex-3	2910	8953;8954;8955	chr2:178769853;178769852;178769851	chr2:179634580;179634579;179634578

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-19
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.1457
• 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
V/I	None	None	0.767	N	0.405	0.213	0.646496053153	gnomAD-4.0.0	1.59049E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85652E-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
V/A	0.9083	likely_pathogenic	0.854	pathogenic	-1.145	Destabilizing	0.998	D	0.664	neutral	N	0.461906376	None	None	N
V/C	0.9781	likely_pathogenic	0.967	pathogenic	-0.628	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
V/D	0.9927	likely_pathogenic	0.9879	pathogenic	-0.987	Destabilizing	1.0	D	0.809	deleterious	D	0.609636141	None	None	N
V/E	0.9712	likely_pathogenic	0.9583	pathogenic	-1.031	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
V/F	0.8686	likely_pathogenic	0.8363	pathogenic	-1.03	Destabilizing	0.999	D	0.818	deleterious	D	0.649143123	None	None	N
V/G	0.9542	likely_pathogenic	0.9283	pathogenic	-1.41	Destabilizing	1.0	D	0.789	deleterious	D	0.649250399	None	None	N
V/H	0.9922	likely_pathogenic	0.9891	pathogenic	-1.049	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
V/I	0.1957	likely_benign	0.1866	benign	-0.538	Destabilizing	0.767	D	0.405	neutral	N	0.518930747	None	None	N
V/K	0.9797	likely_pathogenic	0.9719	pathogenic	-0.966	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
V/L	0.881	likely_pathogenic	0.8484	pathogenic	-0.538	Destabilizing	0.981	D	0.619	neutral	N	0.514075182	None	None	N
V/M	0.8161	likely_pathogenic	0.7568	pathogenic	-0.356	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/N	0.9823	likely_pathogenic	0.9724	pathogenic	-0.607	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
V/P	0.9911	likely_pathogenic	0.9858	pathogenic	-0.705	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/Q	0.9688	likely_pathogenic	0.956	pathogenic	-0.808	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/R	0.9676	likely_pathogenic	0.9587	pathogenic	-0.459	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/S	0.9442	likely_pathogenic	0.9119	pathogenic	-1.031	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
V/T	0.8983	likely_pathogenic	0.8572	pathogenic	-0.967	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
V/W	0.9983	likely_pathogenic	0.9974	pathogenic	-1.191	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/Y	0.9839	likely_pathogenic	0.9792	pathogenic	-0.904	Destabilizing	1.0	D	0.827	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.