TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21762	65509;65510;65511	chr2:178583898;178583897;178583896	chr2:179448625;179448624;179448623
N2AB	20121	60586;60587;60588	chr2:178583898;178583897;178583896	chr2:179448625;179448624;179448623
N2A	19194	57805;57806;57807	chr2:178583898;178583897;178583896	chr2:179448625;179448624;179448623
N2B	12697	38314;38315;38316	chr2:178583898;178583897;178583896	chr2:179448625;179448624;179448623
Novex-1	12822	38689;38690;38691	chr2:178583898;178583897;178583896	chr2:179448625;179448624;179448623
Novex-2	12889	38890;38891;38892	chr2:178583898;178583897;178583896	chr2:179448625;179448624;179448623
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-46
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.1994
• 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
G/R	rs772939753	-0.957	1.0	N	0.821	0.431	0.624040304256	gnomAD-2.1.1	1.93E-05	None	None	None	None	N	None	0	1.36064E-04	None	0	0	None	0	None	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
G/A	0.4372	ambiguous	0.3209	benign	-0.796	Destabilizing	1.0	D	0.605	neutral	D	0.524791486	None	None	N
G/C	0.6465	likely_pathogenic	0.526	ambiguous	-1.046	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
G/D	0.8042	likely_pathogenic	0.7231	pathogenic	-1.286	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
G/E	0.7153	likely_pathogenic	0.5821	pathogenic	-1.342	Destabilizing	1.0	D	0.826	deleterious	N	0.520094955	None	None	N
G/F	0.9629	likely_pathogenic	0.9386	pathogenic	-1.127	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
G/H	0.9226	likely_pathogenic	0.8755	pathogenic	-1.417	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
G/I	0.9042	likely_pathogenic	0.8358	pathogenic	-0.41	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
G/K	0.9039	likely_pathogenic	0.8398	pathogenic	-1.318	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
G/L	0.8874	likely_pathogenic	0.8076	pathogenic	-0.41	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
G/M	0.9081	likely_pathogenic	0.8446	pathogenic	-0.378	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/N	0.8312	likely_pathogenic	0.7472	pathogenic	-1.007	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
G/P	0.9867	likely_pathogenic	0.9771	pathogenic	-0.498	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
G/Q	0.759	likely_pathogenic	0.6509	pathogenic	-1.193	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
G/R	0.8037	likely_pathogenic	0.7164	pathogenic	-1.011	Destabilizing	1.0	D	0.821	deleterious	N	0.477734659	None	None	N
G/S	0.2682	likely_benign	0.2034	benign	-1.267	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
G/T	0.5529	ambiguous	0.4478	ambiguous	-1.243	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
G/V	0.773	likely_pathogenic	0.6645	pathogenic	-0.498	Destabilizing	1.0	D	0.851	deleterious	N	0.491815062	None	None	N
G/W	0.9388	likely_pathogenic	0.909	pathogenic	-1.476	Destabilizing	1.0	D	0.781	deleterious	N	0.520872611	None	None	N
G/Y	0.9448	likely_pathogenic	0.9063	pathogenic	-1.066	Destabilizing	1.0	D	0.843	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.