TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19586	58981;58982;58983	chr2:178593452;178593451;178593450	chr2:179458179;179458178;179458177
N2AB	17945	54058;54059;54060	chr2:178593452;178593451;178593450	chr2:179458179;179458178;179458177
N2A	17018	51277;51278;51279	chr2:178593452;178593451;178593450	chr2:179458179;179458178;179458177
N2B	10521	31786;31787;31788	chr2:178593452;178593451;178593450	chr2:179458179;179458178;179458177
Novex-1	10646	32161;32162;32163	chr2:178593452;178593451;178593450	chr2:179458179;179458178;179458177
Novex-2	10713	32362;32363;32364	chr2:178593452;178593451;178593450	chr2:179458179;179458178;179458177
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-30
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.3175
• 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
P/S	None	None	1.0	D	0.845	0.431	0.482936932564	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	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
P/A	0.8198	likely_pathogenic	0.81	pathogenic	-2.202	Highly Destabilizing	1.0	D	0.851	deleterious	N	0.512274556	None	None	N
P/C	0.9703	likely_pathogenic	0.9669	pathogenic	-2.029	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/D	0.9993	likely_pathogenic	0.9993	pathogenic	-3.029	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
P/E	0.998	likely_pathogenic	0.998	pathogenic	-2.834	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
P/F	0.9982	likely_pathogenic	0.998	pathogenic	-1.268	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/G	0.9892	likely_pathogenic	0.9892	pathogenic	-2.685	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
P/H	0.9979	likely_pathogenic	0.9977	pathogenic	-2.315	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
P/I	0.8343	likely_pathogenic	0.8427	pathogenic	-0.855	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
P/K	0.9986	likely_pathogenic	0.9986	pathogenic	-1.762	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/L	0.6947	likely_pathogenic	0.6821	pathogenic	-0.855	Destabilizing	1.0	D	0.875	deleterious	N	0.489686329	None	None	N
P/M	0.959	likely_pathogenic	0.9552	pathogenic	-1.18	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/N	0.9979	likely_pathogenic	0.998	pathogenic	-2.092	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/Q	0.9964	likely_pathogenic	0.9961	pathogenic	-1.99	Destabilizing	1.0	D	0.855	deleterious	D	0.542749074	None	None	N
P/R	0.9969	likely_pathogenic	0.9969	pathogenic	-1.556	Destabilizing	1.0	D	0.9	deleterious	D	0.531392769	None	None	N
P/S	0.99	likely_pathogenic	0.9895	pathogenic	-2.646	Highly Destabilizing	1.0	D	0.845	deleterious	D	0.531139279	None	None	N
P/T	0.9554	likely_pathogenic	0.9498	pathogenic	-2.322	Highly Destabilizing	1.0	D	0.836	deleterious	N	0.519529484	None	None	N
P/V	0.6545	likely_pathogenic	0.6705	pathogenic	-1.279	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/W	0.9997	likely_pathogenic	0.9997	pathogenic	-1.713	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
P/Y	0.9992	likely_pathogenic	0.9991	pathogenic	-1.395	Destabilizing	1.0	D	0.903	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.