TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7944	24055;24056;24057	chr2:178719662;178719661;178719660	chr2:179584389;179584388;179584387
N2AB	7627	23104;23105;23106	chr2:178719662;178719661;178719660	chr2:179584389;179584388;179584387
N2A	6700	20323;20324;20325	chr2:178719662;178719661;178719660	chr2:179584389;179584388;179584387
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-64
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.0678
• 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/P	None	None	0.984	N	0.782	0.309	0.236278675362	gnomAD-4.0.0	1.59137E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-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	0.6733	likely_pathogenic	0.682	pathogenic	-0.47	Destabilizing	0.076	N	0.487	neutral	None	None	None	None	N
A/D	0.9584	likely_pathogenic	0.9645	pathogenic	-1.599	Destabilizing	0.968	D	0.779	deleterious	N	0.462226254	None	None	N
A/E	0.9321	likely_pathogenic	0.9416	pathogenic	-1.348	Destabilizing	0.976	D	0.786	deleterious	None	None	None	None	N
A/F	0.7268	likely_pathogenic	0.7403	pathogenic	-0.214	Destabilizing	0.996	D	0.778	deleterious	None	None	None	None	N
A/G	0.3194	likely_benign	0.3424	ambiguous	-0.952	Destabilizing	0.811	D	0.729	prob.delet.	N	0.466060108	None	None	N
A/H	0.943	likely_pathogenic	0.9474	pathogenic	-1.72	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
A/I	0.5718	likely_pathogenic	0.6342	pathogenic	1.026	Stabilizing	0.988	D	0.785	deleterious	None	None	None	None	N
A/K	0.9808	likely_pathogenic	0.985	pathogenic	-0.315	Destabilizing	0.976	D	0.785	deleterious	None	None	None	None	N
A/L	0.5356	ambiguous	0.5737	pathogenic	1.026	Stabilizing	0.919	D	0.786	deleterious	None	None	None	None	N
A/M	0.5771	likely_pathogenic	0.6336	pathogenic	0.579	Stabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
A/N	0.899	likely_pathogenic	0.9099	pathogenic	-0.741	Destabilizing	0.976	D	0.771	deleterious	None	None	None	None	N
A/P	0.9683	likely_pathogenic	0.9688	pathogenic	0.59	Stabilizing	0.984	D	0.782	deleterious	N	0.468720714	None	None	N
A/Q	0.917	likely_pathogenic	0.9232	pathogenic	-0.406	Destabilizing	0.988	D	0.793	deleterious	None	None	None	None	N
A/R	0.9622	likely_pathogenic	0.9667	pathogenic	-0.816	Destabilizing	0.976	D	0.793	deleterious	None	None	None	None	N
A/S	0.1711	likely_benign	0.1767	benign	-1.15	Destabilizing	0.046	N	0.472	neutral	N	0.401931272	None	None	N
A/T	0.2003	likely_benign	0.241	benign	-0.747	Destabilizing	0.811	D	0.739	prob.delet.	N	0.482258925	None	None	N
A/V	0.2762	likely_benign	0.3208	benign	0.59	Stabilizing	0.896	D	0.741	deleterious	N	0.455083003	None	None	N
A/W	0.9667	likely_pathogenic	0.9675	pathogenic	-1.094	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
A/Y	0.8801	likely_pathogenic	0.8844	pathogenic	-0.391	Destabilizing	0.996	D	0.787	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.