TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6638	20137;20138;20139	chr2:178727666;178727665;178727664	chr2:179592393;179592392;179592391
N2AB	6321	19186;19187;19188	chr2:178727666;178727665;178727664	chr2:179592393;179592392;179592391
N2A	5394	16405;16406;16407	chr2:178727666;178727665;178727664	chr2:179592393;179592392;179592391
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: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-50
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.5319
• 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/T	rs878890344	None	None	N	0.221	0.095	0.0482279557977	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/T	rs878890344	None	None	N	0.221	0.095	0.0482279557977	gnomAD-4.0.0	3.72E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08783E-06	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	0.4148	ambiguous	0.4686	ambiguous	-0.711	Destabilizing	0.676	D	0.273	neutral	None	None	None	None	N
A/D	0.2131	likely_benign	0.2214	benign	-0.539	Destabilizing	0.029	N	0.345	neutral	N	0.471716644	None	None	N
A/E	0.2158	likely_benign	0.23	benign	-0.692	Destabilizing	0.038	N	0.325	neutral	None	None	None	None	N
A/F	0.2333	likely_benign	0.235	benign	-0.937	Destabilizing	0.214	N	0.361	neutral	None	None	None	None	N
A/G	0.111	likely_benign	0.1108	benign	-0.387	Destabilizing	None	N	0.207	neutral	N	0.439124223	None	None	N
A/H	0.3439	ambiguous	0.3769	ambiguous	-0.44	Destabilizing	0.676	D	0.31	neutral	None	None	None	None	N
A/I	0.158	likely_benign	0.1486	benign	-0.349	Destabilizing	None	N	0.198	neutral	None	None	None	None	N
A/K	0.3259	likely_benign	0.3497	ambiguous	-0.684	Destabilizing	0.038	N	0.324	neutral	None	None	None	None	N
A/L	0.137	likely_benign	0.136	benign	-0.349	Destabilizing	None	N	0.191	neutral	None	None	None	None	N
A/M	0.1842	likely_benign	0.175	benign	-0.338	Destabilizing	0.214	N	0.285	neutral	None	None	None	None	N
A/N	0.1665	likely_benign	0.1719	benign	-0.31	Destabilizing	0.12	N	0.391	neutral	None	None	None	None	N
A/P	0.1231	likely_benign	0.1291	benign	-0.306	Destabilizing	0.171	N	0.337	neutral	N	0.356313625	None	None	N
A/Q	0.2775	likely_benign	0.2986	benign	-0.604	Destabilizing	0.214	N	0.295	neutral	None	None	None	None	N
A/R	0.2981	likely_benign	0.3191	benign	-0.195	Destabilizing	0.214	N	0.32	neutral	None	None	None	None	N
A/S	0.0797	likely_benign	0.0816	benign	-0.515	Destabilizing	None	N	0.103	neutral	N	0.444356684	None	None	N
A/T	0.0762	likely_benign	0.0763	benign	-0.589	Destabilizing	None	N	0.221	neutral	N	0.387791326	None	None	N
A/V	0.0963	likely_benign	0.091	benign	-0.306	Destabilizing	None	N	0.107	neutral	N	0.417804801	None	None	N
A/W	0.5861	likely_pathogenic	0.6268	pathogenic	-1.082	Destabilizing	0.864	D	0.369	neutral	None	None	None	None	N
A/Y	0.325	likely_benign	0.3542	ambiguous	-0.731	Destabilizing	0.356	N	0.334	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.