TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14718	44377;44378;44379	chr2:178630806;178630805;178630804	chr2:179495533;179495532;179495531
N2AB	13077	39454;39455;39456	chr2:178630806;178630805;178630804	chr2:179495533;179495532;179495531
N2A	12150	36673;36674;36675	chr2:178630806;178630805;178630804	chr2:179495533;179495532;179495531
N2B	5653	17182;17183;17184	chr2:178630806;178630805;178630804	chr2:179495533;179495532;179495531
Novex-1	5778	17557;17558;17559	chr2:178630806;178630805;178630804	chr2:179495533;179495532;179495531
Novex-2	5845	17758;17759;17760	chr2:178630806;178630805;178630804	chr2:179495533;179495532;179495531
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-98
• Domain position: 44
• Structural Position: 111
• Q(SASA): 0.6723
• 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
P/L	rs761687390	0.097	0.986	D	0.54	0.403	0.396794106654	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
P/L	rs761687390	0.097	0.986	D	0.54	0.403	0.396794106654	gnomAD-4.0.0	1.37036E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80046E-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
P/A	0.064	likely_benign	0.067	benign	-0.195	Destabilizing	0.058	N	0.402	neutral	N	0.434420089	None	None	N
P/C	0.5937	likely_pathogenic	0.6177	pathogenic	-0.544	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
P/D	0.3548	ambiguous	0.4058	ambiguous	-0.362	Destabilizing	0.995	D	0.579	neutral	None	None	None	None	N
P/E	0.2397	likely_benign	0.2484	benign	-0.496	Destabilizing	0.989	D	0.591	neutral	None	None	None	None	N
P/F	0.5274	ambiguous	0.5766	pathogenic	-0.656	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
P/G	0.2714	likely_benign	0.3362	benign	-0.254	Destabilizing	0.929	D	0.477	neutral	None	None	None	None	N
P/H	0.2089	likely_benign	0.2116	benign	0.077	Stabilizing	0.999	D	0.491	neutral	N	0.476713137	None	None	N
P/I	0.3009	likely_benign	0.3375	benign	-0.192	Destabilizing	0.989	D	0.58	neutral	None	None	None	None	N
P/K	0.241	likely_benign	0.2777	benign	-0.237	Destabilizing	0.989	D	0.593	neutral	None	None	None	None	N
P/L	0.1368	likely_benign	0.1371	benign	-0.192	Destabilizing	0.986	D	0.54	neutral	D	0.541003075	None	None	N
P/M	0.3009	likely_benign	0.3297	benign	-0.328	Destabilizing	1.0	D	0.49	neutral	None	None	None	None	N
P/N	0.286	likely_benign	0.3422	ambiguous	0.043	Stabilizing	0.995	D	0.483	neutral	None	None	None	None	N
P/Q	0.1521	likely_benign	0.1564	benign	-0.218	Destabilizing	0.995	D	0.512	neutral	None	None	None	None	N
P/R	0.1775	likely_benign	0.1752	benign	0.244	Stabilizing	0.993	D	0.455	neutral	N	0.498434639	None	None	N
P/S	0.103	likely_benign	0.1107	benign	-0.235	Destabilizing	0.908	D	0.596	neutral	N	0.434248303	None	None	N
P/T	0.0928	likely_benign	0.0999	benign	-0.281	Destabilizing	0.986	D	0.585	neutral	D	0.537367968	None	None	N
P/V	0.1997	likely_benign	0.2261	benign	-0.163	Destabilizing	0.979	D	0.459	neutral	None	None	None	None	N
P/W	0.6516	likely_pathogenic	0.6893	pathogenic	-0.73	Destabilizing	1.0	D	0.622	neutral	None	None	None	None	N
P/Y	0.4864	ambiguous	0.5393	ambiguous	-0.422	Destabilizing	1.0	D	0.581	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.