TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10043	30352;30353;30354	chr2:178704243;178704242;178704241	chr2:179568970;179568969;179568968
N2AB	9726	29401;29402;29403	chr2:178704243;178704242;178704241	chr2:179568970;179568969;179568968
N2A	8799	26620;26621;26622	chr2:178704243;178704242;178704241	chr2:179568970;179568969;179568968
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: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-85
• Domain position: 55
• Structural Position: 136
• Q(SASA): 0.0838
• 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
H/R	None	None	0.92	None	0.753	0.357	0.166414681773	gnomAD-4.0.0	4.77262E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57251E-06	0	0
H/Y	rs989692401	0.449	0.986	None	0.727	0.363	0.248417906384	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
H/Y	rs989692401	0.449	0.986	None	0.727	0.363	0.248417906384	gnomAD-4.0.0	1.59089E-06	None	None	None	None	N	None	0	2.28624E-05	None	0	0	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
H/A	0.9684	likely_pathogenic	0.9782	pathogenic	-1.781	Destabilizing	0.863	D	0.757	deleterious	None	None	None	None	N
H/C	0.7872	likely_pathogenic	0.85	pathogenic	-1.121	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
H/D	0.9745	likely_pathogenic	0.9819	pathogenic	-1.707	Destabilizing	0.92	D	0.803	deleterious	None	None	None	None	N
H/E	0.9607	likely_pathogenic	0.9766	pathogenic	-1.521	Destabilizing	0.759	D	0.661	neutral	None	None	None	None	N
H/F	0.9178	likely_pathogenic	0.9342	pathogenic	0.167	Stabilizing	0.997	D	0.837	deleterious	None	None	None	None	N
H/G	0.9787	likely_pathogenic	0.9867	pathogenic	-2.159	Highly Destabilizing	0.969	D	0.792	deleterious	None	None	None	None	N
H/I	0.9523	likely_pathogenic	0.972	pathogenic	-0.657	Destabilizing	0.997	D	0.855	deleterious	None	None	None	None	N
H/K	0.962	likely_pathogenic	0.9735	pathogenic	-1.171	Destabilizing	0.884	D	0.779	deleterious	None	None	None	None	N
H/L	0.7379	likely_pathogenic	0.8067	pathogenic	-0.657	Destabilizing	0.92	D	0.806	deleterious	None	None	None	None	N
H/M	0.9492	likely_pathogenic	0.968	pathogenic	-0.956	Destabilizing	0.997	D	0.8	deleterious	None	None	None	None	N
H/N	0.7304	likely_pathogenic	0.8215	pathogenic	-1.713	Destabilizing	0.959	D	0.713	prob.delet.	None	None	None	None	N
H/P	0.9867	likely_pathogenic	0.9909	pathogenic	-1.024	Destabilizing	0.996	D	0.815	deleterious	None	None	None	None	N
H/Q	0.7608	likely_pathogenic	0.8468	pathogenic	-1.308	Destabilizing	0.159	N	0.425	neutral	None	None	None	None	N
H/R	0.8765	likely_pathogenic	0.9134	pathogenic	-1.323	Destabilizing	0.92	D	0.753	deleterious	None	None	None	None	N
H/S	0.9154	likely_pathogenic	0.9419	pathogenic	-1.892	Destabilizing	0.939	D	0.787	deleterious	None	None	None	None	N
H/T	0.9622	likely_pathogenic	0.9777	pathogenic	-1.6	Destabilizing	0.969	D	0.795	deleterious	None	None	None	None	N
H/V	0.9404	likely_pathogenic	0.9635	pathogenic	-1.024	Destabilizing	0.969	D	0.817	deleterious	None	None	None	None	N
H/W	0.9205	likely_pathogenic	0.9485	pathogenic	0.675	Stabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
H/Y	0.7086	likely_pathogenic	0.7726	pathogenic	0.468	Stabilizing	0.986	D	0.727	prob.delet.	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.