TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17233	51922;51923;51924	chr2:178609726;178609725;178609724	chr2:179474453;179474452;179474451
N2AB	15592	46999;47000;47001	chr2:178609726;178609725;178609724	chr2:179474453;179474452;179474451
N2A	14665	44218;44219;44220	chr2:178609726;178609725;178609724	chr2:179474453;179474452;179474451
N2B	8168	24727;24728;24729	chr2:178609726;178609725;178609724	chr2:179474453;179474452;179474451
Novex-1	8293	25102;25103;25104	chr2:178609726;178609725;178609724	chr2:179474453;179474452;179474451
Novex-2	8360	25303;25304;25305	chr2:178609726;178609725;178609724	chr2:179474453;179474452;179474451
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-13
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.2735
• 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/L	rs776803516	-0.858	0.987	N	0.78	0.485	0.648041160416	gnomAD-2.1.1	2.43E-05	None	None	None	None	N	None	0	1.74327E-04	None	0	0	None	0	None	0	0	0
P/L	rs776803516	-0.858	0.987	N	0.78	0.485	0.648041160416	gnomAD-4.0.0	3.431E-06	None	None	None	None	N	None	0	8.96218E-05	None	0	0	None	0	0	9.01933E-07	0	0
P/S	rs761840475	-1.332	0.987	N	0.713	0.446	0.361558571881	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	0	0
P/S	rs761840475	-1.332	0.987	N	0.713	0.446	0.361558571881	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.9478E-04	None	0	0	0	0	0
P/S	rs761840475	-1.332	0.987	N	0.713	0.446	0.361558571881	gnomAD-4.0.0	1.86372E-06	None	None	None	None	N	None	0	0	None	0	4.47227E-05	None	0	0	0	1.10234E-05	0
P/T	rs761840475	-1.325	0.568	N	0.452	0.437	0.343788945184	gnomAD-2.1.1	8.11E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	8.97E-06	0
P/T	rs761840475	-1.325	0.568	N	0.452	0.437	0.343788945184	gnomAD-4.0.0	8.91762E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.17213E-05	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	0.309	likely_benign	0.2524	benign	-1.507	Destabilizing	0.955	D	0.596	neutral	N	0.479038106	None	None	N
P/C	0.9449	likely_pathogenic	0.9372	pathogenic	-0.94	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/D	0.984	likely_pathogenic	0.979	pathogenic	-1.518	Destabilizing	0.995	D	0.785	deleterious	None	None	None	None	N
P/E	0.9583	likely_pathogenic	0.9462	pathogenic	-1.57	Destabilizing	0.995	D	0.769	deleterious	None	None	None	None	N
P/F	0.9557	likely_pathogenic	0.9423	pathogenic	-1.342	Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
P/G	0.9075	likely_pathogenic	0.8844	pathogenic	-1.754	Destabilizing	0.995	D	0.731	prob.delet.	None	None	None	None	N
P/H	0.9097	likely_pathogenic	0.8927	pathogenic	-1.207	Destabilizing	1.0	D	0.843	deleterious	N	0.518591205	None	None	N
P/I	0.9171	likely_pathogenic	0.8867	pathogenic	-0.942	Destabilizing	0.995	D	0.855	deleterious	None	None	None	None	N
P/K	0.9789	likely_pathogenic	0.9727	pathogenic	-1.164	Destabilizing	0.995	D	0.785	deleterious	None	None	None	None	N
P/L	0.8203	likely_pathogenic	0.7726	pathogenic	-0.942	Destabilizing	0.987	D	0.78	deleterious	N	0.506839598	None	None	N
P/M	0.9282	likely_pathogenic	0.9065	pathogenic	-0.652	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/N	0.9703	likely_pathogenic	0.9636	pathogenic	-0.907	Destabilizing	0.995	D	0.811	deleterious	None	None	None	None	N
P/Q	0.9206	likely_pathogenic	0.8985	pathogenic	-1.199	Destabilizing	0.998	D	0.825	deleterious	None	None	None	None	N
P/R	0.9531	likely_pathogenic	0.9406	pathogenic	-0.527	Destabilizing	0.997	D	0.842	deleterious	N	0.504245932	None	None	N
P/S	0.7666	likely_pathogenic	0.7115	pathogenic	-1.345	Destabilizing	0.987	D	0.713	prob.delet.	N	0.498966013	None	None	N
P/T	0.773	likely_pathogenic	0.7308	pathogenic	-1.308	Destabilizing	0.568	D	0.452	neutral	N	0.502688996	None	None	N
P/V	0.8131	likely_pathogenic	0.7704	pathogenic	-1.097	Destabilizing	0.99	D	0.727	prob.delet.	None	None	None	None	N
P/W	0.9816	likely_pathogenic	0.9758	pathogenic	-1.434	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/Y	0.954	likely_pathogenic	0.9391	pathogenic	-1.184	Destabilizing	1.0	D	0.877	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.