TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7446	22561;22562;22563	chr2:178722451;178722450;178722449	chr2:179587178;179587177;179587176
N2AB	7129	21610;21611;21612	chr2:178722451;178722450;178722449	chr2:179587178;179587177;179587176
N2A	6202	18829;18830;18831	chr2:178722451;178722450;178722449	chr2:179587178;179587177;179587176
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-59
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.5636
• 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	0.012	N	0.385	0.151	0.218112801441	gnomAD-4.0.0	1.59196E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.0259E-05

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	0.6146	likely_pathogenic	0.604	pathogenic	-0.901	Destabilizing	0.676	D	0.457	neutral	None	None	None	None	I
A/D	0.1501	likely_benign	0.1731	benign	-0.566	Destabilizing	0.016	N	0.367	neutral	None	None	None	None	I
A/E	0.112	likely_benign	0.1301	benign	-0.708	Destabilizing	None	N	0.087	neutral	N	0.414008506	None	None	I
A/F	0.2534	likely_benign	0.2677	benign	-0.91	Destabilizing	0.356	N	0.462	neutral	None	None	None	None	I
A/G	0.1313	likely_benign	0.1396	benign	-0.301	Destabilizing	0.012	N	0.379	neutral	N	0.480790858	None	None	I
A/H	0.3451	ambiguous	0.3667	ambiguous	-0.233	Destabilizing	0.356	N	0.473	neutral	None	None	None	None	I
A/I	0.1773	likely_benign	0.1955	benign	-0.426	Destabilizing	0.214	N	0.547	neutral	None	None	None	None	I
A/K	0.2587	likely_benign	0.2908	benign	-0.653	Destabilizing	0.016	N	0.427	neutral	None	None	None	None	I
A/L	0.1282	likely_benign	0.1341	benign	-0.426	Destabilizing	0.072	N	0.421	neutral	None	None	None	None	I
A/M	0.1724	likely_benign	0.1857	benign	-0.647	Destabilizing	0.628	D	0.473	neutral	None	None	None	None	I
A/N	0.1877	likely_benign	0.207	benign	-0.368	Destabilizing	0.038	N	0.495	neutral	None	None	None	None	I
A/P	0.125	likely_benign	0.15	benign	-0.352	Destabilizing	None	N	0.161	neutral	N	0.336533865	None	None	I
A/Q	0.2038	likely_benign	0.2265	benign	-0.618	Destabilizing	0.001	N	0.118	neutral	None	None	None	None	I
A/R	0.2708	likely_benign	0.2949	benign	-0.206	Destabilizing	0.072	N	0.495	neutral	None	None	None	None	I
A/S	0.0753	likely_benign	0.0781	benign	-0.556	Destabilizing	None	N	0.059	neutral	N	0.431151472	None	None	I
A/T	0.0733	likely_benign	0.0788	benign	-0.624	Destabilizing	0.012	N	0.385	neutral	N	0.492007929	None	None	I
A/V	0.0943	likely_benign	0.0997	benign	-0.352	Destabilizing	0.055	N	0.353	neutral	N	0.496856389	None	None	I
A/W	0.6493	likely_pathogenic	0.669	pathogenic	-1.014	Destabilizing	0.864	D	0.491	neutral	None	None	None	None	I
A/Y	0.3666	ambiguous	0.3847	ambiguous	-0.704	Destabilizing	0.356	N	0.467	neutral	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.