TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7212	21859;21860;21861	chr2:178723466;178723465;178723464	chr2:179588193;179588192;179588191
N2AB	6895	20908;20909;20910	chr2:178723466;178723465;178723464	chr2:179588193;179588192;179588191
N2A	5968	18127;18128;18129	chr2:178723466;178723465;178723464	chr2:179588193;179588192;179588191
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-56
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.2323
• 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
S/F	None	None	0.794	N	0.563	0.338	0.682465373879	gnomAD-4.0.0	2.05334E-06	None	None	None	None	N	None	2.98954E-05	0	None	0	0	None	0	0	1.79926E-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
S/A	0.0866	likely_benign	0.089	benign	-0.746	Destabilizing	0.001	N	0.129	neutral	N	0.492213696	None	None	N
S/C	0.1329	likely_benign	0.1504	benign	-0.741	Destabilizing	0.936	D	0.478	neutral	D	0.531526533	None	None	N
S/D	0.3791	ambiguous	0.3972	ambiguous	-0.85	Destabilizing	0.418	N	0.401	neutral	None	None	None	None	N
S/E	0.4448	ambiguous	0.4311	ambiguous	-0.829	Destabilizing	0.129	N	0.352	neutral	None	None	None	None	N
S/F	0.1622	likely_benign	0.168	benign	-0.862	Destabilizing	0.794	D	0.563	neutral	N	0.516384792	None	None	N
S/G	0.1134	likely_benign	0.1263	benign	-1.011	Destabilizing	0.129	N	0.353	neutral	None	None	None	None	N
S/H	0.273	likely_benign	0.2623	benign	-1.466	Destabilizing	0.836	D	0.489	neutral	None	None	None	None	N
S/I	0.1796	likely_benign	0.1953	benign	-0.143	Destabilizing	0.01	N	0.459	neutral	None	None	None	None	N
S/K	0.5217	ambiguous	0.5056	ambiguous	-0.84	Destabilizing	0.129	N	0.352	neutral	None	None	None	None	N
S/L	0.1058	likely_benign	0.1167	benign	-0.143	Destabilizing	0.129	N	0.537	neutral	None	None	None	None	N
S/M	0.2097	likely_benign	0.2176	benign	0.097	Stabilizing	0.836	D	0.489	neutral	None	None	None	None	N
S/N	0.1275	likely_benign	0.1377	benign	-0.938	Destabilizing	0.418	N	0.393	neutral	None	None	None	None	N
S/P	0.8371	likely_pathogenic	0.8556	pathogenic	-0.31	Destabilizing	0.523	D	0.497	neutral	D	0.542629349	None	None	N
S/Q	0.423	ambiguous	0.407	ambiguous	-1.107	Destabilizing	0.027	N	0.279	neutral	None	None	None	None	N
S/R	0.3737	ambiguous	0.3706	ambiguous	-0.706	Destabilizing	0.002	N	0.337	neutral	None	None	None	None	N
S/T	0.0764	likely_benign	0.0808	benign	-0.878	Destabilizing	0.007	N	0.147	neutral	N	0.470872148	None	None	N
S/V	0.1937	likely_benign	0.2073	benign	-0.31	Destabilizing	0.129	N	0.541	neutral	None	None	None	None	N
S/W	0.2583	likely_benign	0.251	benign	-0.857	Destabilizing	0.983	D	0.581	neutral	None	None	None	None	N
S/Y	0.1571	likely_benign	0.1597	benign	-0.574	Destabilizing	0.921	D	0.564	neutral	N	0.510700026	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.