TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31524	94795;94796;94797	chr2:178546858;178546857;178546856	chr2:179411585;179411584;179411583
N2AB	29883	89872;89873;89874	chr2:178546858;178546857;178546856	chr2:179411585;179411584;179411583
N2A	28956	87091;87092;87093	chr2:178546858;178546857;178546856	chr2:179411585;179411584;179411583
N2B	22459	67600;67601;67602	chr2:178546858;178546857;178546856	chr2:179411585;179411584;179411583
Novex-1	22584	67975;67976;67977	chr2:178546858;178546857;178546856	chr2:179411585;179411584;179411583
Novex-2	22651	68176;68177;68178	chr2:178546858;178546857;178546856	chr2:179411585;179411584;179411583
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-118
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1346
• 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
S/L	rs796571658	None	0.217	N	0.527	0.33	0.536756967961	gnomAD-4.0.0	3.24899E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.87096E-06	0	0
S/P	rs1697398361	None	0.999	N	0.658	0.447	0.453772157364	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.2323	likely_benign	0.2177	benign	-0.831	Destabilizing	0.987	D	0.449	neutral	N	0.48787068	None	None	N
S/C	0.2672	likely_benign	0.2572	benign	-0.671	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
S/D	0.9035	likely_pathogenic	0.8816	pathogenic	-0.826	Destabilizing	1.0	D	0.568	neutral	None	None	None	None	N
S/E	0.9422	likely_pathogenic	0.9308	pathogenic	-0.727	Destabilizing	0.999	D	0.544	neutral	None	None	None	None	N
S/F	0.7887	likely_pathogenic	0.7499	pathogenic	-0.79	Destabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	N
S/G	0.289	likely_benign	0.2848	benign	-1.16	Destabilizing	0.999	D	0.492	neutral	None	None	None	None	N
S/H	0.73	likely_pathogenic	0.6977	pathogenic	-1.544	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
S/I	0.794	likely_pathogenic	0.7909	pathogenic	-0.033	Destabilizing	0.995	D	0.627	neutral	None	None	None	None	N
S/K	0.9649	likely_pathogenic	0.9584	pathogenic	-0.478	Destabilizing	0.999	D	0.526	neutral	None	None	None	None	N
S/L	0.477	ambiguous	0.436	ambiguous	-0.033	Destabilizing	0.217	N	0.527	neutral	N	0.500010471	None	None	N
S/M	0.5733	likely_pathogenic	0.5549	ambiguous	0.04	Stabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
S/N	0.4994	ambiguous	0.4706	ambiguous	-0.8	Destabilizing	1.0	D	0.554	neutral	None	None	None	None	N
S/P	0.9936	likely_pathogenic	0.9926	pathogenic	-0.265	Destabilizing	0.999	D	0.658	neutral	N	0.491919029	None	None	N
S/Q	0.8444	likely_pathogenic	0.824	pathogenic	-0.792	Destabilizing	1.0	D	0.602	neutral	None	None	None	None	N
S/R	0.9407	likely_pathogenic	0.9309	pathogenic	-0.603	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
S/T	0.1639	likely_benign	0.1611	benign	-0.665	Destabilizing	0.994	D	0.502	neutral	N	0.391610783	None	None	N
S/V	0.7059	likely_pathogenic	0.6864	pathogenic	-0.265	Destabilizing	0.983	D	0.583	neutral	None	None	None	None	N
S/W	0.8518	likely_pathogenic	0.8351	pathogenic	-0.861	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
S/Y	0.6963	likely_pathogenic	0.6484	pathogenic	-0.511	Destabilizing	1.0	D	0.74	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.