TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32430	97513;97514;97515	chr2:178542468;178542467;178542466	chr2:179407195;179407194;179407193
N2AB	30789	92590;92591;92592	chr2:178542468;178542467;178542466	chr2:179407195;179407194;179407193
N2A	29862	89809;89810;89811	chr2:178542468;178542467;178542466	chr2:179407195;179407194;179407193
N2B	23365	70318;70319;70320	chr2:178542468;178542467;178542466	chr2:179407195;179407194;179407193
Novex-1	23490	70693;70694;70695	chr2:178542468;178542467;178542466	chr2:179407195;179407194;179407193
Novex-2	23557	70894;70895;70896	chr2:178542468;178542467;178542466	chr2:179407195;179407194;179407193
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-124
• Domain position: 32
• Structural Position: 33
• Q(SASA): 0.1412
• Predicted PPI site: I

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
A/T	None	None	1.0	N	0.773	0.35	0.40032279838	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.6402	likely_pathogenic	0.6587	pathogenic	-0.73	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
A/D	0.9612	likely_pathogenic	0.9554	pathogenic	-0.642	Destabilizing	1.0	D	0.851	deleterious	N	0.521116462	None	None	I
A/E	0.9482	likely_pathogenic	0.942	pathogenic	-0.693	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
A/F	0.7955	likely_pathogenic	0.7917	pathogenic	-0.913	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
A/G	0.4203	ambiguous	0.3938	ambiguous	-0.966	Destabilizing	1.0	D	0.629	neutral	N	0.475589242	None	None	I
A/H	0.9123	likely_pathogenic	0.9124	pathogenic	-1.092	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
A/I	0.7712	likely_pathogenic	0.7476	pathogenic	-0.283	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
A/K	0.9773	likely_pathogenic	0.9757	pathogenic	-0.931	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
A/L	0.6469	likely_pathogenic	0.6223	pathogenic	-0.283	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
A/M	0.6802	likely_pathogenic	0.6498	pathogenic	-0.268	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
A/N	0.8331	likely_pathogenic	0.8252	pathogenic	-0.598	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
A/P	0.9777	likely_pathogenic	0.9786	pathogenic	-0.393	Destabilizing	1.0	D	0.846	deleterious	N	0.491741219	None	None	I
A/Q	0.8661	likely_pathogenic	0.8641	pathogenic	-0.756	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
A/R	0.9439	likely_pathogenic	0.9419	pathogenic	-0.613	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
A/S	0.1512	likely_benign	0.1502	benign	-0.966	Destabilizing	1.0	D	0.661	neutral	N	0.417391875	None	None	I
A/T	0.3595	ambiguous	0.3258	benign	-0.915	Destabilizing	1.0	D	0.773	deleterious	N	0.506013724	None	None	I
A/V	0.4951	ambiguous	0.4583	ambiguous	-0.393	Destabilizing	1.0	D	0.703	prob.neutral	N	0.481963428	None	None	I
A/W	0.9805	likely_pathogenic	0.9806	pathogenic	-1.206	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
A/Y	0.9057	likely_pathogenic	0.9054	pathogenic	-0.803	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I

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.