TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9604	29035;29036;29037	chr2:178707757;178707756;178707755	chr2:179572484;179572483;179572482
N2AB	9287	28084;28085;28086	chr2:178707757;178707756;178707755	chr2:179572484;179572483;179572482
N2A	8360	25303;25304;25305	chr2:178707757;178707756;178707755	chr2:179572484;179572483;179572482
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-82
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.3139
• 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/E	rs1469017379	-0.569	1.0	None	0.801	0.704	0.809385375033	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
G/E	rs1469017379	-0.569	1.0	None	0.801	0.704	0.809385375033	gnomAD-4.0.0	3.18275E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71729E-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
G/A	0.3476	ambiguous	0.3017	benign	-0.399	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
G/C	0.6069	likely_pathogenic	0.5841	pathogenic	-0.889	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
G/D	0.2922	likely_benign	0.2471	benign	-0.759	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
G/E	0.3689	ambiguous	0.3177	benign	-0.929	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/F	0.8802	likely_pathogenic	0.8507	pathogenic	-1.145	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
G/H	0.654	likely_pathogenic	0.6059	pathogenic	-0.639	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/I	0.8233	likely_pathogenic	0.7784	pathogenic	-0.539	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
G/K	0.558	ambiguous	0.523	ambiguous	-0.888	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/L	0.7963	likely_pathogenic	0.7532	pathogenic	-0.539	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
G/M	0.8185	likely_pathogenic	0.7648	pathogenic	-0.455	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/N	0.3772	ambiguous	0.3368	benign	-0.537	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/P	0.9622	likely_pathogenic	0.958	pathogenic	-0.46	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/Q	0.5555	ambiguous	0.4933	ambiguous	-0.865	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
G/R	0.4802	ambiguous	0.4267	ambiguous	-0.395	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/S	0.2109	likely_benign	0.1849	benign	-0.665	Destabilizing	0.993	D	0.577	neutral	None	None	None	None	N
G/T	0.4359	ambiguous	0.3939	ambiguous	-0.773	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
G/V	0.6737	likely_pathogenic	0.6149	pathogenic	-0.46	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
G/W	0.7085	likely_pathogenic	0.6491	pathogenic	-1.277	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
G/Y	0.7464	likely_pathogenic	0.7029	pathogenic	-0.939	Destabilizing	1.0	D	0.829	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.