TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8893	26902;26903;26904	chr2:178713981;178713980;178713979	chr2:179578708;179578707;179578706
N2AB	8576	25951;25952;25953	chr2:178713981;178713980;178713979	chr2:179578708;179578707;179578706
N2A	7649	23170;23171;23172	chr2:178713981;178713980;178713979	chr2:179578708;179578707;179578706
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-74
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.2263
• 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
A/V	rs1353521188	-0.303	None	N	0.275	0.123	0.364730456448	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	0	0
A/V	rs1353521188	-0.303	None	N	0.275	0.123	0.364730456448	gnomAD-4.0.0	1.59172E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88324E-05	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
A/C	0.3688	ambiguous	0.3648	ambiguous	-0.899	Destabilizing	0.676	D	0.397	neutral	None	None	None	None	N
A/D	0.1286	likely_benign	0.1342	benign	-0.945	Destabilizing	0.038	N	0.411	neutral	None	None	None	None	N
A/E	0.1247	likely_benign	0.125	benign	-1.069	Destabilizing	None	N	0.13	neutral	N	0.383503879	None	None	N
A/F	0.1848	likely_benign	0.1862	benign	-1.262	Destabilizing	0.214	N	0.457	neutral	None	None	None	None	N
A/G	0.0957	likely_benign	0.0878	benign	-0.818	Destabilizing	None	N	0.13	neutral	N	0.459369862	None	None	N
A/H	0.2679	likely_benign	0.2641	benign	-0.881	Destabilizing	0.356	N	0.444	neutral	None	None	None	None	N
A/I	0.1445	likely_benign	0.1611	benign	-0.563	Destabilizing	0.013	N	0.397	neutral	None	None	None	None	N
A/K	0.2216	likely_benign	0.2234	benign	-0.872	Destabilizing	0.038	N	0.388	neutral	None	None	None	None	N
A/L	0.0954	likely_benign	0.0999	benign	-0.563	Destabilizing	0.038	N	0.381	neutral	None	None	None	None	N
A/M	0.1262	likely_benign	0.1393	benign	-0.363	Destabilizing	0.214	N	0.389	neutral	None	None	None	None	N
A/N	0.1389	likely_benign	0.1358	benign	-0.577	Destabilizing	0.072	N	0.425	neutral	None	None	None	None	N
A/P	0.3944	ambiguous	0.4683	ambiguous	-0.573	Destabilizing	0.295	N	0.386	neutral	D	0.535945134	None	None	N
A/Q	0.186	likely_benign	0.1757	benign	-0.891	Destabilizing	0.12	N	0.381	neutral	None	None	None	None	N
A/R	0.2259	likely_benign	0.2236	benign	-0.402	Destabilizing	0.214	N	0.375	neutral	None	None	None	None	N
A/S	0.0672	likely_benign	0.0646	benign	-0.837	Destabilizing	0.001	N	0.192	neutral	N	0.393414229	None	None	N
A/T	0.0651	likely_benign	0.0684	benign	-0.884	Destabilizing	None	N	0.106	neutral	N	0.406708813	None	None	N
A/V	0.0854	likely_benign	0.094	benign	-0.573	Destabilizing	None	N	0.275	neutral	N	0.448134148	None	None	N
A/W	0.5331	ambiguous	0.5497	ambiguous	-1.417	Destabilizing	0.864	D	0.527	neutral	None	None	None	None	N
A/Y	0.2942	likely_benign	0.3029	benign	-1.051	Destabilizing	0.356	N	0.463	neutral	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.