TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9627	29104;29105;29106	chr2:178707688;178707687;178707686	chr2:179572415;179572414;179572413
N2AB	9310	28153;28154;28155	chr2:178707688;178707687;178707686	chr2:179572415;179572414;179572413
N2A	8383	25372;25373;25374	chr2:178707688;178707687;178707686	chr2:179572415;179572414;179572413
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-82
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.4264
• 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
G/D	rs878908638	-0.18	0.994	None	0.381	0.475	0.31501682445	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.66E-05	0
G/D	rs878908638	-0.18	0.994	None	0.381	0.475	0.31501682445	gnomAD-4.0.0	2.73669E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59769E-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
G/A	0.4283	ambiguous	0.3135	benign	-0.28	Destabilizing	0.961	D	0.407	neutral	None	None	None	None	N
G/C	0.7535	likely_pathogenic	0.6077	pathogenic	-1.021	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
G/D	0.6741	likely_pathogenic	0.4153	ambiguous	-0.602	Destabilizing	0.994	D	0.381	neutral	None	None	None	None	N
G/E	0.6847	likely_pathogenic	0.4369	ambiguous	-0.752	Destabilizing	0.97	D	0.459	neutral	None	None	None	None	N
G/F	0.9345	likely_pathogenic	0.8554	pathogenic	-0.972	Destabilizing	0.996	D	0.611	neutral	None	None	None	None	N
G/H	0.8266	likely_pathogenic	0.6728	pathogenic	-0.348	Destabilizing	0.191	N	0.382	neutral	None	None	None	None	N
G/I	0.8808	likely_pathogenic	0.7463	pathogenic	-0.48	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
G/K	0.8313	likely_pathogenic	0.6242	pathogenic	-0.806	Destabilizing	0.942	D	0.453	neutral	None	None	None	None	N
G/L	0.8753	likely_pathogenic	0.7603	pathogenic	-0.48	Destabilizing	0.991	D	0.581	neutral	None	None	None	None	N
G/M	0.8909	likely_pathogenic	0.7884	pathogenic	-0.698	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
G/N	0.5598	ambiguous	0.4085	ambiguous	-0.527	Destabilizing	0.97	D	0.393	neutral	None	None	None	None	N
G/P	0.9799	likely_pathogenic	0.9576	pathogenic	-0.386	Destabilizing	0.999	D	0.523	neutral	None	None	None	None	N
G/Q	0.6702	likely_pathogenic	0.4693	ambiguous	-0.773	Destabilizing	0.991	D	0.523	neutral	None	None	None	None	N
G/R	0.6763	likely_pathogenic	0.4348	ambiguous	-0.373	Destabilizing	0.031	N	0.309	neutral	None	None	None	None	N
G/S	0.1993	likely_benign	0.1494	benign	-0.674	Destabilizing	0.98	D	0.373	neutral	None	None	None	None	N
G/T	0.5896	likely_pathogenic	0.435	ambiguous	-0.754	Destabilizing	0.996	D	0.485	neutral	None	None	None	None	N
G/V	0.7648	likely_pathogenic	0.585	pathogenic	-0.386	Destabilizing	0.994	D	0.608	neutral	None	None	None	None	N
G/W	0.8561	likely_pathogenic	0.7182	pathogenic	-1.095	Destabilizing	1.0	D	0.596	neutral	None	None	None	None	N
G/Y	0.8814	likely_pathogenic	0.7749	pathogenic	-0.782	Destabilizing	0.991	D	0.605	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.