TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6412	19459;19460;19461	chr2:178728692;178728691;178728690	chr2:179593419;179593418;179593417
N2AB	6095	18508;18509;18510	chr2:178728692;178728691;178728690	chr2:179593419;179593418;179593417
N2A	5168	15727;15728;15729	chr2:178728692;178728691;178728690	chr2:179593419;179593418;179593417
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: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-48
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.6785
• Predicted PPI site: I

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/Q	None	None	1.0	D	0.636	0.753	0.631970868704	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.93751E-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
P/A	0.7815	likely_pathogenic	0.6518	pathogenic	-0.61	Destabilizing	0.996	D	0.593	neutral	D	0.531172409	None	None	I
P/C	0.9925	likely_pathogenic	0.9878	pathogenic	-0.632	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
P/D	0.9805	likely_pathogenic	0.9651	pathogenic	-0.266	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	I
P/E	0.9542	likely_pathogenic	0.9176	pathogenic	-0.349	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	I
P/F	0.9969	likely_pathogenic	0.9945	pathogenic	-0.668	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
P/G	0.9433	likely_pathogenic	0.9029	pathogenic	-0.781	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	I
P/H	0.9668	likely_pathogenic	0.9456	pathogenic	-0.253	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	I
P/I	0.9831	likely_pathogenic	0.9733	pathogenic	-0.293	Destabilizing	0.998	D	0.633	neutral	None	None	None	None	I
P/K	0.9691	likely_pathogenic	0.9449	pathogenic	-0.498	Destabilizing	1.0	D	0.632	neutral	None	None	None	None	I
P/L	0.915	likely_pathogenic	0.8775	pathogenic	-0.293	Destabilizing	0.998	D	0.638	neutral	D	0.619439865	None	None	I
P/M	0.9772	likely_pathogenic	0.9613	pathogenic	-0.425	Destabilizing	1.0	D	0.624	neutral	None	None	None	None	I
P/N	0.9799	likely_pathogenic	0.9593	pathogenic	-0.235	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
P/Q	0.9342	likely_pathogenic	0.88	pathogenic	-0.44	Destabilizing	1.0	D	0.636	neutral	D	0.552074594	None	None	I
P/R	0.9302	likely_pathogenic	0.8862	pathogenic	0.003	Stabilizing	1.0	D	0.655	neutral	D	0.644574368	None	None	I
P/S	0.9171	likely_pathogenic	0.84	pathogenic	-0.643	Destabilizing	0.999	D	0.635	neutral	D	0.54021131	None	None	I
P/T	0.8581	likely_pathogenic	0.7724	pathogenic	-0.618	Destabilizing	0.999	D	0.635	neutral	D	0.577478784	None	None	I
P/V	0.9486	likely_pathogenic	0.9175	pathogenic	-0.363	Destabilizing	0.91	D	0.338	neutral	None	None	None	None	I
P/W	0.9967	likely_pathogenic	0.9946	pathogenic	-0.75	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
P/Y	0.9944	likely_pathogenic	0.9903	pathogenic	-0.462	Destabilizing	1.0	D	0.668	neutral	None	None	None	None	I

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.