TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16581	49966;49967;49968	chr2:178612980;178612979;178612978	chr2:179477707;179477706;179477705
N2AB	14940	45043;45044;45045	chr2:178612980;178612979;178612978	chr2:179477707;179477706;179477705
N2A	14013	42262;42263;42264	chr2:178612980;178612979;178612978	chr2:179477707;179477706;179477705
N2B	7516	22771;22772;22773	chr2:178612980;178612979;178612978	chr2:179477707;179477706;179477705
Novex-1	7641	23146;23147;23148	chr2:178612980;178612979;178612978	chr2:179477707;179477706;179477705
Novex-2	7708	23347;23348;23349	chr2:178612980;178612979;178612978	chr2:179477707;179477706;179477705
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: Fn3-8
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2128
• 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	1.0	N	0.771	0.365	0.37953744168	gnomAD-4.0.0	2.73841E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59925E-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	0.6337	likely_pathogenic	0.6045	pathogenic	-0.78	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
A/D	0.7069	likely_pathogenic	0.8786	pathogenic	-0.956	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
A/E	0.6007	likely_pathogenic	0.8063	pathogenic	-1.093	Destabilizing	1.0	D	0.828	deleterious	N	0.477302736	None	None	N
A/F	0.6552	likely_pathogenic	0.7651	pathogenic	-1.166	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
A/G	0.271	likely_benign	0.3147	benign	-0.736	Destabilizing	1.0	D	0.634	neutral	N	0.468623472	None	None	N
A/H	0.7929	likely_pathogenic	0.8671	pathogenic	-0.819	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
A/I	0.7113	likely_pathogenic	0.8262	pathogenic	-0.495	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/K	0.8729	likely_pathogenic	0.9588	pathogenic	-0.897	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
A/L	0.4681	ambiguous	0.57	pathogenic	-0.495	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
A/M	0.493	ambiguous	0.5953	pathogenic	-0.295	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
A/N	0.6418	likely_pathogenic	0.7503	pathogenic	-0.504	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
A/P	0.9819	likely_pathogenic	0.9921	pathogenic	-0.5	Destabilizing	1.0	D	0.83	deleterious	D	0.629800602	None	None	N
A/Q	0.6285	likely_pathogenic	0.7518	pathogenic	-0.833	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/R	0.7908	likely_pathogenic	0.9198	pathogenic	-0.392	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
A/S	0.13	likely_benign	0.1302	benign	-0.734	Destabilizing	1.0	D	0.658	neutral	N	0.423726843	None	None	N
A/T	0.242	likely_benign	0.3309	benign	-0.797	Destabilizing	1.0	D	0.771	deleterious	N	0.474075315	None	None	N
A/V	0.4131	ambiguous	0.5531	ambiguous	-0.5	Destabilizing	1.0	D	0.71	prob.delet.	N	0.500683274	None	None	N
A/W	0.922	likely_pathogenic	0.9576	pathogenic	-1.32	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
A/Y	0.8013	likely_pathogenic	0.8791	pathogenic	-0.971	Destabilizing	1.0	D	0.837	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.