TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14959	45100;45101;45102	chr2:178622708;178622707;178622706	chr2:179487435;179487434;179487433
N2AB	13318	40177;40178;40179	chr2:178622708;178622707;178622706	chr2:179487435;179487434;179487433
N2A	12391	37396;37397;37398	chr2:178622708;178622707;178622706	chr2:179487435;179487434;179487433
N2B	5894	17905;17906;17907	chr2:178622708;178622707;178622706	chr2:179487435;179487434;179487433
Novex-1	6019	18280;18281;18282	chr2:178622708;178622707;178622706	chr2:179487435;179487434;179487433
Novex-2	6086	18481;18482;18483	chr2:178622708;178622707;178622706	chr2:179487435;179487434;179487433
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-101
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.0849
• 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
A/T	None	None	0.999	D	0.757	0.316	0.301122078929	gnomAD-4.0.0	6.86992E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01671E-07	0	0
A/V	None	None	0.999	N	0.683	0.348	0.275215494804	gnomAD-4.0.0	1.60627E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.45904E-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
A/C	0.8438	likely_pathogenic	0.8598	pathogenic	-0.889	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
A/D	0.9895	likely_pathogenic	0.9843	pathogenic	-1.901	Destabilizing	0.999	D	0.852	deleterious	D	0.669450772	None	None	N
A/E	0.978	likely_pathogenic	0.9701	pathogenic	-1.713	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/F	0.9519	likely_pathogenic	0.9424	pathogenic	-0.69	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
A/G	0.2545	likely_benign	0.276	benign	-1.483	Destabilizing	0.275	N	0.349	neutral	D	0.558524481	None	None	N
A/H	0.9923	likely_pathogenic	0.99	pathogenic	-1.878	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
A/I	0.7621	likely_pathogenic	0.7801	pathogenic	0.278	Stabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
A/K	0.9923	likely_pathogenic	0.9904	pathogenic	-1.194	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
A/L	0.6715	likely_pathogenic	0.6789	pathogenic	0.278	Stabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
A/M	0.8469	likely_pathogenic	0.8442	pathogenic	0.154	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
A/N	0.9789	likely_pathogenic	0.9734	pathogenic	-1.367	Destabilizing	0.999	D	0.844	deleterious	None	None	None	None	N
A/P	0.9676	likely_pathogenic	0.954	pathogenic	-0.103	Destabilizing	1.0	D	0.865	deleterious	D	0.669325244	None	None	N
A/Q	0.9719	likely_pathogenic	0.9666	pathogenic	-1.192	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
A/R	0.9804	likely_pathogenic	0.9743	pathogenic	-1.281	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
A/S	0.4558	ambiguous	0.438	ambiguous	-1.822	Destabilizing	0.992	D	0.566	neutral	D	0.59095534	None	None	N
A/T	0.5312	ambiguous	0.5444	ambiguous	-1.492	Destabilizing	0.999	D	0.757	deleterious	D	0.537593534	None	None	N
A/V	0.4099	ambiguous	0.4273	ambiguous	-0.103	Destabilizing	0.999	D	0.683	prob.neutral	N	0.440872356	None	None	N
A/W	0.9972	likely_pathogenic	0.996	pathogenic	-1.41	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
A/Y	0.9857	likely_pathogenic	0.9811	pathogenic	-0.815	Destabilizing	1.0	D	0.863	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.