TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27136	81631;81632;81633	chr2:178564726;178564725;178564724	chr2:179429453;179429452;179429451
N2AB	25495	76708;76709;76710	chr2:178564726;178564725;178564724	chr2:179429453;179429452;179429451
N2A	24568	73927;73928;73929	chr2:178564726;178564725;178564724	chr2:179429453;179429452;179429451
N2B	18071	54436;54437;54438	chr2:178564726;178564725;178564724	chr2:179429453;179429452;179429451
Novex-1	18196	54811;54812;54813	chr2:178564726;178564725;178564724	chr2:179429453;179429452;179429451
Novex-2	18263	55012;55013;55014	chr2:178564726;178564725;178564724	chr2:179429453;179429452;179429451
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-85
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.5111
• 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/A	rs879200560	None	0.201	N	0.368	0.229	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
G/A	rs879200560	None	0.201	N	0.368	0.229	None	gnomAD-4.0.0	2.47974E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39107E-05	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	0.1359	likely_benign	0.1646	benign	-0.379	Destabilizing	0.201	N	0.368	neutral	N	0.488292314	None	None	N
G/C	0.173	likely_benign	0.1899	benign	-0.886	Destabilizing	0.992	D	0.56	neutral	None	None	None	None	N
G/D	0.2289	likely_benign	0.2455	benign	-0.645	Destabilizing	0.005	N	0.262	neutral	None	None	None	None	N
G/E	0.2811	likely_benign	0.3172	benign	-0.803	Destabilizing	0.016	N	0.336	neutral	N	0.507115376	None	None	N
G/F	0.5078	ambiguous	0.5584	ambiguous	-1.069	Destabilizing	0.92	D	0.53	neutral	None	None	None	None	N
G/H	0.3216	likely_benign	0.3459	ambiguous	-0.644	Destabilizing	0.977	D	0.468	neutral	None	None	None	None	N
G/I	0.3427	ambiguous	0.3857	ambiguous	-0.468	Destabilizing	0.85	D	0.526	neutral	None	None	None	None	N
G/K	0.4013	ambiguous	0.4431	ambiguous	-0.913	Destabilizing	0.617	D	0.423	neutral	None	None	None	None	N
G/L	0.3911	ambiguous	0.455	ambiguous	-0.468	Destabilizing	0.739	D	0.489	neutral	None	None	None	None	N
G/M	0.4148	ambiguous	0.4514	ambiguous	-0.47	Destabilizing	0.977	D	0.527	neutral	None	None	None	None	N
G/N	0.1764	likely_benign	0.1859	benign	-0.548	Destabilizing	0.021	N	0.267	neutral	None	None	None	None	N
G/P	0.7918	likely_pathogenic	0.849	pathogenic	-0.404	Destabilizing	0.92	D	0.457	neutral	None	None	None	None	N
G/Q	0.3008	likely_benign	0.3321	benign	-0.838	Destabilizing	0.85	D	0.465	neutral	None	None	None	None	N
G/R	0.2925	likely_benign	0.3301	benign	-0.447	Destabilizing	0.81	D	0.462	neutral	N	0.512465267	None	None	N
G/S	0.0982	likely_benign	0.1055	benign	-0.701	Destabilizing	0.447	N	0.355	neutral	None	None	None	None	N
G/T	0.1725	likely_benign	0.1969	benign	-0.788	Destabilizing	0.005	N	0.329	neutral	None	None	None	None	N
G/V	0.247	likely_benign	0.2881	benign	-0.404	Destabilizing	0.681	D	0.494	neutral	N	0.518677927	None	None	N
G/W	0.4302	ambiguous	0.4574	ambiguous	-1.232	Destabilizing	0.99	D	0.558	neutral	D	0.530541211	None	None	N
G/Y	0.3733	ambiguous	0.4015	ambiguous	-0.881	Destabilizing	0.972	D	0.529	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.