TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5161	15706;15707;15708	chr2:178734343;178734342;178734341	chr2:179599070;179599069;179599068
N2AB	4844	14755;14756;14757	chr2:178734343;178734342;178734341	chr2:179599070;179599069;179599068
N2A	3917	11974;11975;11976	chr2:178734343;178734342;178734341	chr2:179599070;179599069;179599068
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: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-34
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.2949
• 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
T/I	rs1205352955	0.163	0.201	N	0.564	0.299	None	gnomAD-2.1.1	4.15E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.11E-06	0
T/I	rs1205352955	0.163	0.201	N	0.564	0.299	None	gnomAD-4.0.0	2.0775E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.81574E-06	0	1.67768E-05
T/N	None	None	0.379	N	0.543	0.255	0.532311620844	gnomAD-4.0.0	6.92501E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.07871E-07	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
T/A	0.0643	likely_benign	0.0678	benign	-0.67	Destabilizing	0.201	N	0.343	neutral	N	0.497550326	None	None	N
T/C	0.2688	likely_benign	0.3259	benign	-0.408	Destabilizing	0.992	D	0.527	neutral	None	None	None	None	N
T/D	0.2259	likely_benign	0.271	benign	-0.295	Destabilizing	0.617	D	0.522	neutral	None	None	None	None	N
T/E	0.1718	likely_benign	0.1982	benign	-0.279	Destabilizing	0.617	D	0.519	neutral	None	None	None	None	N
T/F	0.1326	likely_benign	0.1478	benign	-0.589	Destabilizing	0.85	D	0.583	neutral	None	None	None	None	N
T/G	0.1375	likely_benign	0.1714	benign	-0.952	Destabilizing	0.447	N	0.567	neutral	None	None	None	None	N
T/H	0.1435	likely_benign	0.1625	benign	-1.243	Destabilizing	0.977	D	0.551	neutral	None	None	None	None	N
T/I	0.0961	likely_benign	0.1064	benign	-0.002	Destabilizing	0.201	N	0.564	neutral	N	0.497344833	None	None	N
T/K	0.1046	likely_benign	0.1151	benign	-0.845	Destabilizing	0.447	N	0.509	neutral	None	None	None	None	N
T/L	0.0751	likely_benign	0.0801	benign	-0.002	Destabilizing	0.005	N	0.261	neutral	None	None	None	None	N
T/M	0.0848	likely_benign	0.0863	benign	0.124	Stabilizing	0.85	D	0.563	neutral	None	None	None	None	N
T/N	0.0809	likely_benign	0.0899	benign	-0.744	Destabilizing	0.379	N	0.543	neutral	N	0.495831727	None	None	N
T/P	0.084	likely_benign	0.0993	benign	-0.192	Destabilizing	0.004	N	0.323	neutral	N	0.493115375	None	None	N
T/Q	0.1299	likely_benign	0.1409	benign	-0.829	Destabilizing	0.85	D	0.579	neutral	None	None	None	None	N
T/R	0.0915	likely_benign	0.0932	benign	-0.668	Destabilizing	0.85	D	0.575	neutral	None	None	None	None	N
T/S	0.0733	likely_benign	0.0808	benign	-0.966	Destabilizing	0.016	N	0.22	neutral	N	0.490221254	None	None	N
T/V	0.0865	likely_benign	0.0947	benign	-0.192	Destabilizing	0.009	N	0.196	neutral	None	None	None	None	N
T/W	0.3831	ambiguous	0.44	ambiguous	-0.596	Destabilizing	0.992	D	0.573	neutral	None	None	None	None	N
T/Y	0.1671	likely_benign	0.1947	benign	-0.371	Destabilizing	0.972	D	0.574	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.