TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5171	15736;15737;15738	chr2:178733878;178733877;178733876	chr2:179598605;179598604;179598603
N2AB	4854	14785;14786;14787	chr2:178733878;178733877;178733876	chr2:179598605;179598604;179598603
N2A	3927	12004;12005;12006	chr2:178733878;178733877;178733876	chr2:179598605;179598604;179598603
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-35
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.5972
• 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/L	rs776104290	-0.126	0.002	N	0.073	0.095	0.207176502487	gnomAD-2.1.1	4.13E-06	None	None	None	None	N	None	0	3E-05	None	0	0	None	0	None	0	0	0
V/L	rs776104290	-0.126	0.002	N	0.073	0.095	0.207176502487	gnomAD-4.0.0	1.63143E-06	None	None	None	None	N	None	0	2.34478E-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
V/A	0.2185	likely_benign	0.253	benign	-0.577	Destabilizing	0.201	N	0.264	neutral	N	0.499238031	None	None	N
V/C	0.7417	likely_pathogenic	0.7876	pathogenic	-0.679	Destabilizing	0.992	D	0.337	neutral	None	None	None	None	N
V/D	0.4613	ambiguous	0.4808	ambiguous	-0.278	Destabilizing	0.85	D	0.387	neutral	None	None	None	None	N
V/E	0.3209	likely_benign	0.3254	benign	-0.363	Destabilizing	0.549	D	0.385	neutral	N	0.499449923	None	None	N
V/F	0.1667	likely_benign	0.1912	benign	-0.613	Destabilizing	0.739	D	0.393	neutral	None	None	None	None	N
V/G	0.2427	likely_benign	0.2861	benign	-0.75	Destabilizing	0.549	D	0.398	neutral	D	0.597351659	None	None	N
V/H	0.5768	likely_pathogenic	0.6303	pathogenic	-0.21	Destabilizing	0.992	D	0.365	neutral	None	None	None	None	N
V/I	0.0707	likely_benign	0.0756	benign	-0.26	Destabilizing	0.004	N	0.125	neutral	N	0.446899472	None	None	N
V/K	0.4478	ambiguous	0.4708	ambiguous	-0.569	Destabilizing	0.617	D	0.359	neutral	None	None	None	None	N
V/L	0.1467	likely_benign	0.1655	benign	-0.26	Destabilizing	0.002	N	0.073	neutral	N	0.44679994	None	None	N
V/M	0.154	likely_benign	0.1732	benign	-0.384	Destabilizing	0.85	D	0.361	neutral	None	None	None	None	N
V/N	0.3466	ambiguous	0.394	ambiguous	-0.35	Destabilizing	0.85	D	0.389	neutral	None	None	None	None	N
V/P	0.7617	likely_pathogenic	0.8256	pathogenic	-0.33	Destabilizing	0.92	D	0.399	neutral	None	None	None	None	N
V/Q	0.3157	likely_benign	0.3471	ambiguous	-0.551	Destabilizing	0.92	D	0.388	neutral	None	None	None	None	N
V/R	0.3908	ambiguous	0.4084	ambiguous	-0.049	Destabilizing	0.92	D	0.407	neutral	None	None	None	None	N
V/S	0.2309	likely_benign	0.2708	benign	-0.757	Destabilizing	0.059	N	0.198	neutral	None	None	None	None	N
V/T	0.1915	likely_benign	0.2263	benign	-0.736	Destabilizing	0.021	N	0.098	neutral	None	None	None	None	N
V/W	0.7464	likely_pathogenic	0.8062	pathogenic	-0.712	Destabilizing	0.992	D	0.429	neutral	None	None	None	None	N
V/Y	0.5196	ambiguous	0.5877	pathogenic	-0.422	Destabilizing	0.92	D	0.373	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.