TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9784	29575;29576;29577	chr2:178706524;178706523;178706522	chr2:179571251;179571250;179571249
N2AB	9467	28624;28625;28626	chr2:178706524;178706523;178706522	chr2:179571251;179571250;179571249
N2A	8540	25843;25844;25845	chr2:178706524;178706523;178706522	chr2:179571251;179571250;179571249
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-83
• Domain position: 87
• Structural Position: 172
• Q(SASA): 0.0967
• 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
V/I	rs2075899130	None	0.001	None	0.114	0.12	0.315314060047	gnomAD-4.0.0	2.05255E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.4785E-05	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
V/A	0.4436	ambiguous	0.2968	benign	-1.853	Destabilizing	0.001	N	0.127	neutral	None	None	None	None	N
V/C	0.8756	likely_pathogenic	0.8353	pathogenic	-1.451	Destabilizing	0.836	D	0.716	prob.delet.	None	None	None	None	N
V/D	0.9899	likely_pathogenic	0.9697	pathogenic	-2.015	Highly Destabilizing	0.351	N	0.797	deleterious	None	None	None	None	N
V/E	0.9835	likely_pathogenic	0.9512	pathogenic	-1.843	Destabilizing	0.418	N	0.73	prob.delet.	None	None	None	None	N
V/F	0.8754	likely_pathogenic	0.746	pathogenic	-1.151	Destabilizing	0.655	D	0.759	deleterious	None	None	None	None	N
V/G	0.7551	likely_pathogenic	0.5523	ambiguous	-2.359	Highly Destabilizing	0.213	N	0.709	prob.delet.	None	None	None	None	N
V/H	0.9954	likely_pathogenic	0.986	pathogenic	-2.052	Highly Destabilizing	0.983	D	0.741	deleterious	None	None	None	None	N
V/I	0.227	likely_benign	0.1658	benign	-0.473	Destabilizing	0.001	N	0.114	neutral	None	None	None	None	N
V/K	0.9907	likely_pathogenic	0.9709	pathogenic	-1.434	Destabilizing	0.418	N	0.737	prob.delet.	None	None	None	None	N
V/L	0.8724	likely_pathogenic	0.7273	pathogenic	-0.473	Destabilizing	0.037	N	0.414	neutral	None	None	None	None	N
V/M	0.7833	likely_pathogenic	0.5775	pathogenic	-0.519	Destabilizing	0.716	D	0.657	neutral	None	None	None	None	N
V/N	0.9726	likely_pathogenic	0.9247	pathogenic	-1.612	Destabilizing	0.716	D	0.799	deleterious	None	None	None	None	N
V/P	0.9966	likely_pathogenic	0.9914	pathogenic	-0.902	Destabilizing	0.836	D	0.773	deleterious	None	None	None	None	N
V/Q	0.9789	likely_pathogenic	0.9389	pathogenic	-1.52	Destabilizing	0.836	D	0.749	deleterious	None	None	None	None	N
V/R	0.9786	likely_pathogenic	0.9417	pathogenic	-1.241	Destabilizing	0.836	D	0.795	deleterious	None	None	None	None	N
V/S	0.7655	likely_pathogenic	0.5816	pathogenic	-2.288	Highly Destabilizing	0.027	N	0.477	neutral	None	None	None	None	N
V/T	0.6037	likely_pathogenic	0.4084	ambiguous	-1.97	Destabilizing	0.004	N	0.139	neutral	None	None	None	None	N
V/W	0.9983	likely_pathogenic	0.9942	pathogenic	-1.582	Destabilizing	0.983	D	0.741	deleterious	None	None	None	None	N
V/Y	0.9904	likely_pathogenic	0.9766	pathogenic	-1.19	Destabilizing	0.836	D	0.751	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.