TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5539	16840;16841;16842	chr2:178732446;178732445;178732444	chr2:179597173;179597172;179597171
N2AB	5222	15889;15890;15891	chr2:178732446;178732445;178732444	chr2:179597173;179597172;179597171
N2A	4295	13108;13109;13110	chr2:178732446;178732445;178732444	chr2:179597173;179597172;179597171
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-38
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.4253
• 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/A	rs773371925	-1.545	0.999	D	0.753	0.754	0.835049036447	gnomAD-2.1.1	4.15E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.07E-06	0
V/A	rs773371925	-1.545	0.999	D	0.753	0.754	0.835049036447	gnomAD-4.0.0	3.25629E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.92613E-06	0	3.08985E-05
V/I	rs2154310288	None	0.997	N	0.722	0.427	0.721577736743	gnomAD-4.0.0	1.6287E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.47584E-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	0.768	likely_pathogenic	0.8336	pathogenic	-2.119	Highly Destabilizing	0.999	D	0.753	deleterious	D	0.638020166	None	None	N
V/C	0.9488	likely_pathogenic	0.9648	pathogenic	-1.911	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/D	0.9935	likely_pathogenic	0.996	pathogenic	-2.771	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/E	0.9751	likely_pathogenic	0.9824	pathogenic	-2.611	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.622374053	None	None	N
V/F	0.8323	likely_pathogenic	0.8931	pathogenic	-1.318	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/G	0.8856	likely_pathogenic	0.9245	pathogenic	-2.583	Highly Destabilizing	1.0	D	0.836	deleterious	D	0.638625579	None	None	N
V/H	0.9927	likely_pathogenic	0.9956	pathogenic	-2.155	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
V/I	0.102	likely_benign	0.1057	benign	-0.848	Destabilizing	0.997	D	0.722	prob.delet.	N	0.498838239	None	None	N
V/K	0.9856	likely_pathogenic	0.9903	pathogenic	-1.684	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/L	0.6488	likely_pathogenic	0.7025	pathogenic	-0.848	Destabilizing	0.997	D	0.758	deleterious	D	0.57796096	None	None	N
V/M	0.6983	likely_pathogenic	0.7836	pathogenic	-1.031	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/N	0.976	likely_pathogenic	0.9861	pathogenic	-1.924	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/P	0.9521	likely_pathogenic	0.9618	pathogenic	-1.245	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/Q	0.9683	likely_pathogenic	0.9786	pathogenic	-1.885	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
V/R	0.9704	likely_pathogenic	0.9771	pathogenic	-1.392	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/S	0.8834	likely_pathogenic	0.921	pathogenic	-2.518	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/T	0.8053	likely_pathogenic	0.8642	pathogenic	-2.231	Highly Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
V/W	0.9952	likely_pathogenic	0.9974	pathogenic	-1.725	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
V/Y	0.986	likely_pathogenic	0.9913	pathogenic	-1.405	Destabilizing	1.0	D	0.891	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.