TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5763	17512;17513;17514	chr2:178731479;178731478;178731477	chr2:179596206;179596205;179596204
N2AB	5446	16561;16562;16563	chr2:178731479;178731478;178731477	chr2:179596206;179596205;179596204
N2A	4519	13780;13781;13782	chr2:178731479;178731478;178731477	chr2:179596206;179596205;179596204
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: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-41
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.103
• 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
W/R	rs897659304	None	0.999	D	0.866	0.951	0.939118346112	gnomAD-4.0.0	1.59156E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85847E-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
W/A	0.9948	likely_pathogenic	0.9939	pathogenic	-3.266	Highly Destabilizing	0.992	D	0.847	deleterious	None	None	None	None	N
W/C	0.9961	likely_pathogenic	0.9956	pathogenic	-1.897	Destabilizing	1.0	D	0.838	deleterious	D	0.655936028	None	None	N
W/D	0.9997	likely_pathogenic	0.9996	pathogenic	-3.565	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
W/E	0.9996	likely_pathogenic	0.9995	pathogenic	-3.459	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
W/F	0.5757	likely_pathogenic	0.532	ambiguous	-1.976	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
W/G	0.9861	likely_pathogenic	0.9838	pathogenic	-3.497	Highly Destabilizing	0.217	N	0.704	prob.neutral	D	0.671753584	None	None	N
W/H	0.9976	likely_pathogenic	0.997	pathogenic	-2.296	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
W/I	0.9671	likely_pathogenic	0.9618	pathogenic	-2.371	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
W/K	0.9998	likely_pathogenic	0.9997	pathogenic	-2.603	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
W/L	0.9132	likely_pathogenic	0.9104	pathogenic	-2.371	Highly Destabilizing	0.999	D	0.843	deleterious	D	0.671753584	None	None	N
W/M	0.9853	likely_pathogenic	0.9838	pathogenic	-1.816	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
W/N	0.9994	likely_pathogenic	0.9992	pathogenic	-3.297	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
W/P	0.9992	likely_pathogenic	0.999	pathogenic	-2.699	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
W/Q	0.9997	likely_pathogenic	0.9996	pathogenic	-3.168	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
W/R	0.9994	likely_pathogenic	0.9992	pathogenic	-2.238	Highly Destabilizing	0.999	D	0.866	deleterious	D	0.671955389	None	None	N
W/S	0.9939	likely_pathogenic	0.9933	pathogenic	-3.451	Highly Destabilizing	0.997	D	0.847	deleterious	D	0.671955389	None	None	N
W/T	0.9962	likely_pathogenic	0.9954	pathogenic	-3.277	Highly Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
W/V	0.9686	likely_pathogenic	0.9662	pathogenic	-2.699	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
W/Y	0.9124	likely_pathogenic	0.8998	pathogenic	-1.852	Destabilizing	1.0	D	0.749	deleterious	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.