TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17330	52213;52214;52215	chr2:178609322;178609321;178609320	chr2:179474049;179474048;179474047
N2AB	15689	47290;47291;47292	chr2:178609322;178609321;178609320	chr2:179474049;179474048;179474047
N2A	14762	44509;44510;44511	chr2:178609322;178609321;178609320	chr2:179474049;179474048;179474047
N2B	8265	25018;25019;25020	chr2:178609322;178609321;178609320	chr2:179474049;179474048;179474047
Novex-1	8390	25393;25394;25395	chr2:178609322;178609321;178609320	chr2:179474049;179474048;179474047
Novex-2	8457	25594;25595;25596	chr2:178609322;178609321;178609320	chr2:179474049;179474048;179474047
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-112
• Domain position: 80
• Structural Position: 134
• Q(SASA): 0.1415
• 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/V	None	None	0.999	N	0.793	0.455	0.543120768234	gnomAD-4.0.0	1.37218E-06	None	None	None	None	N	None	0	2.25723E-05	None	0	0	None	0	0	9.01024E-07	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	0.3606	ambiguous	0.3847	ambiguous	-0.402	Destabilizing	0.992	D	0.693	prob.neutral	N	0.487414303	None	None	N
G/C	0.5385	ambiguous	0.564	ambiguous	-0.893	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
G/D	0.3324	likely_benign	0.354	ambiguous	0.026	Stabilizing	0.538	D	0.46	neutral	None	None	None	None	N
G/E	0.4134	ambiguous	0.4615	ambiguous	-0.067	Destabilizing	0.467	N	0.582	neutral	N	0.483312926	None	None	N
G/F	0.8151	likely_pathogenic	0.8338	pathogenic	-0.829	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
G/H	0.6761	likely_pathogenic	0.7246	pathogenic	-0.803	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
G/I	0.7768	likely_pathogenic	0.8143	pathogenic	-0.208	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
G/K	0.7146	likely_pathogenic	0.7808	pathogenic	-0.727	Destabilizing	0.996	D	0.781	deleterious	None	None	None	None	N
G/L	0.7782	likely_pathogenic	0.8007	pathogenic	-0.208	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
G/M	0.7586	likely_pathogenic	0.7694	pathogenic	-0.391	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
G/N	0.3855	ambiguous	0.4295	ambiguous	-0.395	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
G/P	0.9611	likely_pathogenic	0.9612	pathogenic	-0.233	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
G/Q	0.5833	likely_pathogenic	0.6435	pathogenic	-0.54	Destabilizing	0.998	D	0.804	deleterious	None	None	None	None	N
G/R	0.6352	likely_pathogenic	0.7038	pathogenic	-0.509	Destabilizing	0.998	D	0.807	deleterious	N	0.496443659	None	None	N
G/S	0.2556	likely_benign	0.2844	benign	-0.742	Destabilizing	0.994	D	0.738	prob.delet.	None	None	None	None	N
G/T	0.4712	ambiguous	0.4993	ambiguous	-0.728	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
G/V	0.6441	likely_pathogenic	0.6845	pathogenic	-0.233	Destabilizing	0.999	D	0.793	deleterious	N	0.487733926	None	None	N
G/W	0.6624	likely_pathogenic	0.6645	pathogenic	-1.068	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
G/Y	0.6416	likely_pathogenic	0.6711	pathogenic	-0.656	Destabilizing	1.0	D	0.795	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.