TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16917	50974;50975;50976	chr2:178611480;178611479;178611478	chr2:179476207;179476206;179476205
N2AB	15276	46051;46052;46053	chr2:178611480;178611479;178611478	chr2:179476207;179476206;179476205
N2A	14349	43270;43271;43272	chr2:178611480;178611479;178611478	chr2:179476207;179476206;179476205
N2B	7852	23779;23780;23781	chr2:178611480;178611479;178611478	chr2:179476207;179476206;179476205
Novex-1	7977	24154;24155;24156	chr2:178611480;178611479;178611478	chr2:179476207;179476206;179476205
Novex-2	8044	24355;24356;24357	chr2:178611480;178611479;178611478	chr2:179476207;179476206;179476205
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-11
• Domain position: 66
• Structural Position: 96
• Q(SASA): 0.5186
• 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/D	None	None	1.0	N	0.766	0.46	0.445107144611	gnomAD-4.0.0	1.59294E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86131E-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	0.2026	likely_benign	0.2573	benign	-0.318	Destabilizing	0.998	D	0.532	neutral	D	0.631710727	None	None	N
G/C	0.39	ambiguous	0.4935	ambiguous	-0.777	Destabilizing	1.0	D	0.725	prob.delet.	D	0.649821746	None	None	N
G/D	0.3963	ambiguous	0.4446	ambiguous	-0.907	Destabilizing	1.0	D	0.766	deleterious	N	0.481450091	None	None	N
G/E	0.4869	ambiguous	0.5586	ambiguous	-1.002	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/F	0.7523	likely_pathogenic	0.8501	pathogenic	-0.881	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
G/H	0.7075	likely_pathogenic	0.7842	pathogenic	-0.622	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
G/I	0.4974	ambiguous	0.6388	pathogenic	-0.254	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
G/K	0.8191	likely_pathogenic	0.8645	pathogenic	-0.925	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
G/L	0.6523	likely_pathogenic	0.774	pathogenic	-0.254	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
G/M	0.5917	likely_pathogenic	0.7157	pathogenic	-0.54	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
G/N	0.3519	ambiguous	0.4337	ambiguous	-0.591	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
G/P	0.9071	likely_pathogenic	0.95	pathogenic	-0.241	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
G/Q	0.6667	likely_pathogenic	0.7469	pathogenic	-0.794	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
G/R	0.7656	likely_pathogenic	0.8007	pathogenic	-0.55	Destabilizing	1.0	D	0.772	deleterious	N	0.495787004	None	None	N
G/S	0.1764	likely_benign	0.1893	benign	-0.701	Destabilizing	0.991	D	0.528	neutral	D	0.528236334	None	None	N
G/T	0.2574	likely_benign	0.3174	benign	-0.722	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
G/V	0.3644	ambiguous	0.4703	ambiguous	-0.241	Destabilizing	1.0	D	0.793	deleterious	D	0.709633408	None	None	N
G/W	0.6841	likely_pathogenic	0.8018	pathogenic	-1.13	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
G/Y	0.6354	likely_pathogenic	0.7698	pathogenic	-0.736	Destabilizing	1.0	D	0.791	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.