TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7254	21985;21986;21987	chr2:178723247;178723246;178723245	chr2:179587974;179587973;179587972
N2AB	6937	21034;21035;21036	chr2:178723247;178723246;178723245	chr2:179587974;179587973;179587972
N2A	6010	18253;18254;18255	chr2:178723247;178723246;178723245	chr2:179587974;179587973;179587972
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-57
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.4588
• 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
T/A	rs1230527204	None	None	N	0.083	0.186	0.1749357433	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
T/A	rs1230527204	None	None	N	0.083	0.186	0.1749357433	gnomAD-4.0.0	3.09882E-06	None	None	None	None	I	None	0	1.66756E-05	None	0	0	None	0	0	2.54302E-06	1.09801E-05	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
T/A	0.0684	likely_benign	0.0701	benign	-0.499	Destabilizing	None	N	0.083	neutral	N	0.491250207	None	None	I
T/C	0.2885	likely_benign	0.2799	benign	-0.405	Destabilizing	0.676	D	0.343	neutral	None	None	None	None	I
T/D	0.3138	likely_benign	0.3351	benign	0.683	Stabilizing	0.038	N	0.377	neutral	None	None	None	None	I
T/E	0.2156	likely_benign	0.2192	benign	0.663	Stabilizing	0.038	N	0.312	neutral	None	None	None	None	I
T/F	0.1534	likely_benign	0.1643	benign	-0.833	Destabilizing	0.214	N	0.405	neutral	None	None	None	None	I
T/G	0.1808	likely_benign	0.1826	benign	-0.687	Destabilizing	0.016	N	0.309	neutral	None	None	None	None	I
T/H	0.1706	likely_benign	0.1707	benign	-0.868	Destabilizing	0.356	N	0.355	neutral	None	None	None	None	I
T/I	0.1058	likely_benign	0.1136	benign	-0.112	Destabilizing	0.029	N	0.337	neutral	N	0.494215159	None	None	I
T/K	0.1234	likely_benign	0.1284	benign	-0.189	Destabilizing	None	N	0.146	neutral	None	None	None	None	I
T/L	0.0815	likely_benign	0.084	benign	-0.112	Destabilizing	None	N	0.167	neutral	None	None	None	None	I
T/M	0.0826	likely_benign	0.0834	benign	-0.149	Destabilizing	0.214	N	0.359	neutral	None	None	None	None	I
T/N	0.1083	likely_benign	0.1169	benign	-0.142	Destabilizing	0.029	N	0.323	neutral	N	0.487480436	None	None	I
T/P	0.463	ambiguous	0.4571	ambiguous	-0.211	Destabilizing	0.055	N	0.414	neutral	N	0.516713961	None	None	I
T/Q	0.1592	likely_benign	0.1556	benign	-0.233	Destabilizing	0.12	N	0.415	neutral	None	None	None	None	I
T/R	0.0861	likely_benign	0.0897	benign	-0.054	Destabilizing	0.038	N	0.377	neutral	None	None	None	None	I
T/S	0.0802	likely_benign	0.0825	benign	-0.467	Destabilizing	None	N	0.099	neutral	N	0.461754019	None	None	I
T/V	0.1041	likely_benign	0.1059	benign	-0.211	Destabilizing	0.016	N	0.245	neutral	None	None	None	None	I
T/W	0.4176	ambiguous	0.4034	ambiguous	-0.814	Destabilizing	0.864	D	0.407	neutral	None	None	None	None	I
T/Y	0.1978	likely_benign	0.1972	benign	-0.514	Destabilizing	0.356	N	0.404	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.