TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22057	66394;66395;66396	chr2:178582200;178582199;178582198	chr2:179446927;179446926;179446925
N2AB	20416	61471;61472;61473	chr2:178582200;178582199;178582198	chr2:179446927;179446926;179446925
N2A	19489	58690;58691;58692	chr2:178582200;178582199;178582198	chr2:179446927;179446926;179446925
N2B	12992	39199;39200;39201	chr2:178582200;178582199;178582198	chr2:179446927;179446926;179446925
Novex-1	13117	39574;39575;39576	chr2:178582200;178582199;178582198	chr2:179446927;179446926;179446925
Novex-2	13184	39775;39776;39777	chr2:178582200;178582199;178582198	chr2:179446927;179446926;179446925
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: Fn3-48
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.1871
• 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	None	None	1.0	N	0.89	0.493	0.528260413467	gnomAD-4.0.0	1.61757E-06	None	None	None	None	N	None	5.96944E-05	0	None	0	0	None	0	0	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	0.3724	ambiguous	0.295	benign	-0.749	Destabilizing	0.999	D	0.751	deleterious	N	0.521500464	None	None	N
G/C	0.7311	likely_pathogenic	0.5451	ambiguous	-1.042	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
G/D	0.635	likely_pathogenic	0.5189	ambiguous	-1.582	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
G/E	0.7474	likely_pathogenic	0.6209	pathogenic	-1.689	Destabilizing	1.0	D	0.901	deleterious	N	0.496834093	None	None	N
G/F	0.9666	likely_pathogenic	0.9241	pathogenic	-1.358	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
G/H	0.91	likely_pathogenic	0.8177	pathogenic	-1.192	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
G/I	0.9435	likely_pathogenic	0.8658	pathogenic	-0.58	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
G/K	0.9238	likely_pathogenic	0.858	pathogenic	-1.169	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
G/L	0.8885	likely_pathogenic	0.8111	pathogenic	-0.58	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
G/M	0.9356	likely_pathogenic	0.8791	pathogenic	-0.403	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
G/N	0.7724	likely_pathogenic	0.6582	pathogenic	-0.861	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
G/P	0.9925	likely_pathogenic	0.9883	pathogenic	-0.6	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
G/Q	0.8292	likely_pathogenic	0.72	pathogenic	-1.177	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
G/R	0.8726	likely_pathogenic	0.7627	pathogenic	-0.756	Destabilizing	1.0	D	0.89	deleterious	N	0.491763991	None	None	N
G/S	0.2079	likely_benign	0.1513	benign	-1.013	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
G/T	0.595	likely_pathogenic	0.4463	ambiguous	-1.063	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
G/V	0.8753	likely_pathogenic	0.7476	pathogenic	-0.6	Destabilizing	1.0	D	0.824	deleterious	N	0.492777949	None	None	N
G/W	0.9513	likely_pathogenic	0.8753	pathogenic	-1.59	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
G/Y	0.9372	likely_pathogenic	0.8646	pathogenic	-1.216	Destabilizing	1.0	D	0.884	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.