TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6391	19396;19397;19398	chr2:178728755;178728754;178728753	chr2:179593482;179593481;179593480
N2AB	6074	18445;18446;18447	chr2:178728755;178728754;178728753	chr2:179593482;179593481;179593480
N2A	5147	15664;15665;15666	chr2:178728755;178728754;178728753	chr2:179593482;179593481;179593480
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-48
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2184
• 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/S	None	None	0.045	N	0.433	0.073	0.0666544352282	gnomAD-4.0.0	3.24138E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.87075E-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
A/C	0.7162	likely_pathogenic	0.6342	pathogenic	-0.775	Destabilizing	0.992	D	0.636	neutral	None	None	None	None	N
A/D	0.8635	likely_pathogenic	0.8366	pathogenic	-1.059	Destabilizing	0.549	D	0.685	prob.neutral	N	0.465366675	None	None	N
A/E	0.7438	likely_pathogenic	0.7283	pathogenic	-1.125	Destabilizing	0.617	D	0.656	neutral	None	None	None	None	N
A/F	0.7838	likely_pathogenic	0.6856	pathogenic	-1.042	Destabilizing	0.85	D	0.688	prob.neutral	None	None	None	None	N
A/G	0.3026	likely_benign	0.2608	benign	-1.043	Destabilizing	0.549	D	0.561	neutral	N	0.494996148	None	None	N
A/H	0.9302	likely_pathogenic	0.8993	pathogenic	-1.271	Destabilizing	0.992	D	0.649	neutral	None	None	None	None	N
A/I	0.5244	ambiguous	0.4029	ambiguous	-0.38	Destabilizing	0.739	D	0.721	prob.delet.	None	None	None	None	N
A/K	0.9253	likely_pathogenic	0.9076	pathogenic	-1.193	Destabilizing	0.617	D	0.655	neutral	None	None	None	None	N
A/L	0.3814	ambiguous	0.2689	benign	-0.38	Destabilizing	0.447	N	0.589	neutral	None	None	None	None	N
A/M	0.435	ambiguous	0.3221	benign	-0.251	Destabilizing	0.25	N	0.533	neutral	None	None	None	None	N
A/N	0.7526	likely_pathogenic	0.6792	pathogenic	-0.804	Destabilizing	0.85	D	0.703	prob.neutral	None	None	None	None	N
A/P	0.2146	likely_benign	0.2031	benign	-0.486	Destabilizing	0.002	N	0.383	neutral	N	0.311018479	None	None	N
A/Q	0.7784	likely_pathogenic	0.7422	pathogenic	-0.996	Destabilizing	0.92	D	0.715	prob.delet.	None	None	None	None	N
A/R	0.8842	likely_pathogenic	0.865	pathogenic	-0.816	Destabilizing	0.92	D	0.725	prob.delet.	None	None	None	None	N
A/S	0.2181	likely_benign	0.1905	benign	-1.102	Destabilizing	0.045	N	0.433	neutral	N	0.422018542	None	None	N
A/T	0.176	likely_benign	0.1273	benign	-1.077	Destabilizing	0.379	N	0.589	neutral	N	0.471580571	None	None	N
A/V	0.2336	likely_benign	0.1826	benign	-0.486	Destabilizing	0.379	N	0.584	neutral	N	0.461536936	None	None	N
A/W	0.9509	likely_pathogenic	0.927	pathogenic	-1.35	Destabilizing	0.992	D	0.709	prob.delet.	None	None	None	None	N
A/Y	0.884	likely_pathogenic	0.829	pathogenic	-0.969	Destabilizing	0.972	D	0.663	neutral	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.