TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25669	77230;77231;77232	chr2:178569127;178569126;178569125	chr2:179433854;179433853;179433852
N2AB	24028	72307;72308;72309	chr2:178569127;178569126;178569125	chr2:179433854;179433853;179433852
N2A	23101	69526;69527;69528	chr2:178569127;178569126;178569125	chr2:179433854;179433853;179433852
N2B	16604	50035;50036;50037	chr2:178569127;178569126;178569125	chr2:179433854;179433853;179433852
Novex-1	16729	50410;50411;50412	chr2:178569127;178569126;178569125	chr2:179433854;179433853;179433852
Novex-2	16796	50611;50612;50613	chr2:178569127;178569126;178569125	chr2:179433854;179433853;179433852
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-74
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.1616
• 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
C/S	None	None	0.03	N	0.197	0.226	0.49336223678	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	0	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
C/A	0.2807	likely_benign	0.3229	benign	-1.723	Destabilizing	0.184	N	0.263	neutral	None	None	None	None	N
C/D	0.7186	likely_pathogenic	0.7285	pathogenic	-0.148	Destabilizing	0.528	D	0.504	neutral	None	None	None	None	N
C/E	0.8193	likely_pathogenic	0.8287	pathogenic	-0.044	Destabilizing	0.771	D	0.513	neutral	None	None	None	None	N
C/F	0.1915	likely_benign	0.2107	benign	-1.089	Destabilizing	0.98	D	0.506	neutral	N	0.468873569	None	None	N
C/G	0.1337	likely_benign	0.1554	benign	-2.028	Highly Destabilizing	0.001	N	0.228	neutral	N	0.453718034	None	None	N
C/H	0.4689	ambiguous	0.4898	ambiguous	-1.926	Destabilizing	0.986	D	0.528	neutral	None	None	None	None	N
C/I	0.4401	ambiguous	0.4648	ambiguous	-0.941	Destabilizing	0.9	D	0.505	neutral	None	None	None	None	N
C/K	0.7899	likely_pathogenic	0.807	pathogenic	-0.838	Destabilizing	0.9	D	0.503	neutral	None	None	None	None	N
C/L	0.4058	ambiguous	0.4211	ambiguous	-0.941	Destabilizing	0.65	D	0.404	neutral	None	None	None	None	N
C/M	0.5141	ambiguous	0.5381	ambiguous	-0.082	Destabilizing	0.995	D	0.489	neutral	None	None	None	None	N
C/N	0.3024	likely_benign	0.3399	benign	-0.852	Destabilizing	0.706	D	0.509	neutral	None	None	None	None	N
C/P	0.9787	likely_pathogenic	0.9772	pathogenic	-1.176	Destabilizing	0.888	D	0.549	neutral	None	None	None	None	N
C/Q	0.5523	ambiguous	0.5801	pathogenic	-0.744	Destabilizing	0.96	D	0.549	neutral	None	None	None	None	N
C/R	0.5268	ambiguous	0.5444	ambiguous	-0.693	Destabilizing	0.96	D	0.555	neutral	N	0.444461046	None	None	N
C/S	0.1624	likely_benign	0.1935	benign	-1.433	Destabilizing	0.03	N	0.197	neutral	N	0.442652892	None	None	N
C/T	0.3312	likely_benign	0.372	ambiguous	-1.141	Destabilizing	0.003	N	0.193	neutral	None	None	None	None	N
C/V	0.3798	ambiguous	0.3938	ambiguous	-1.176	Destabilizing	0.628	D	0.428	neutral	None	None	None	None	N
C/W	0.5786	likely_pathogenic	0.5929	pathogenic	-1.054	Destabilizing	0.998	D	0.478	neutral	D	0.523289976	None	None	N
C/Y	0.2944	likely_benign	0.3198	benign	-1.046	Destabilizing	0.993	D	0.511	neutral	D	0.523116617	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.