TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33695	101308;101309;101310	chr2:178535532;178535531;178535530	chr2:179400259;179400258;179400257
N2AB	32054	96385;96386;96387	chr2:178535532;178535531;178535530	chr2:179400259;179400258;179400257
N2A	31127	93604;93605;93606	chr2:178535532;178535531;178535530	chr2:179400259;179400258;179400257
N2B	24630	74113;74114;74115	chr2:178535532;178535531;178535530	chr2:179400259;179400258;179400257
Novex-1	24755	74488;74489;74490	chr2:178535532;178535531;178535530	chr2:179400259;179400258;179400257
Novex-2	24822	74689;74690;74691	chr2:178535532;178535531;178535530	chr2:179400259;179400258;179400257
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-132
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.3343
• 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
G/E	rs1553499879	None	1.0	N	0.819	0.285	0.401327265625	gnomAD-4.0.0	2.73678E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69833E-06	1.15934E-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
G/A	0.1376	likely_benign	0.167	benign	-0.398	Destabilizing	0.788	D	0.412	neutral	N	0.429342452	None	None	N
G/C	0.2479	likely_benign	0.2862	benign	-0.878	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
G/D	0.1644	likely_benign	0.1634	benign	-0.559	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
G/E	0.248	likely_benign	0.2279	benign	-0.704	Destabilizing	1.0	D	0.819	deleterious	N	0.468938203	None	None	N
G/F	0.6022	likely_pathogenic	0.6569	pathogenic	-1.004	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/H	0.4687	ambiguous	0.4888	ambiguous	-0.74	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
G/I	0.4498	ambiguous	0.4413	ambiguous	-0.417	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
G/K	0.6373	likely_pathogenic	0.5835	pathogenic	-0.958	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
G/L	0.4604	ambiguous	0.5427	ambiguous	-0.417	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/M	0.5042	ambiguous	0.5707	pathogenic	-0.442	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
G/N	0.1948	likely_benign	0.226	benign	-0.586	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
G/P	0.9458	likely_pathogenic	0.9244	pathogenic	-0.374	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
G/Q	0.4142	ambiguous	0.4217	ambiguous	-0.845	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
G/R	0.5393	ambiguous	0.4808	ambiguous	-0.544	Destabilizing	1.0	D	0.833	deleterious	N	0.461742872	None	None	N
G/S	0.1125	likely_benign	0.1319	benign	-0.766	Destabilizing	0.995	D	0.647	neutral	None	None	None	None	N
G/T	0.2381	likely_benign	0.2373	benign	-0.835	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/V	0.3163	likely_benign	0.31	benign	-0.374	Destabilizing	1.0	D	0.805	deleterious	N	0.497260955	None	None	N
G/W	0.5743	likely_pathogenic	0.5857	pathogenic	-1.199	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
G/Y	0.474	ambiguous	0.5046	ambiguous	-0.839	Destabilizing	1.0	D	0.814	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.