TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30024	90295;90296;90297	chr2:178552830;178552829;178552828	chr2:179417557;179417556;179417555
N2AB	28383	85372;85373;85374	chr2:178552830;178552829;178552828	chr2:179417557;179417556;179417555
N2A	27456	82591;82592;82593	chr2:178552830;178552829;178552828	chr2:179417557;179417556;179417555
N2B	20959	63100;63101;63102	chr2:178552830;178552829;178552828	chr2:179417557;179417556;179417555
Novex-1	21084	63475;63476;63477	chr2:178552830;178552829;178552828	chr2:179417557;179417556;179417555
Novex-2	21151	63676;63677;63678	chr2:178552830;178552829;178552828	chr2:179417557;179417556;179417555
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: Fn3-106
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.3302
• 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/A	None	None	0.999	N	0.803	0.28	0.28297238246	gnomAD-4.0.0	1.36844E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15934E-05	1.6564E-05

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	0.0816	likely_benign	0.081	benign	-1.162	Destabilizing	0.999	D	0.803	deleterious	N	0.460870506	None	None	N
P/C	0.7659	likely_pathogenic	0.7131	pathogenic	-0.646	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
P/D	0.9489	likely_pathogenic	0.931	pathogenic	-0.736	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
P/E	0.8002	likely_pathogenic	0.7685	pathogenic	-0.713	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/F	0.8967	likely_pathogenic	0.8467	pathogenic	-0.775	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
P/G	0.5801	likely_pathogenic	0.5507	ambiguous	-1.494	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/H	0.7468	likely_pathogenic	0.6893	pathogenic	-1.026	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
P/I	0.6503	likely_pathogenic	0.5629	ambiguous	-0.354	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/K	0.8722	likely_pathogenic	0.8317	pathogenic	-0.893	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
P/L	0.433	ambiguous	0.348	ambiguous	-0.354	Destabilizing	1.0	D	0.857	deleterious	N	0.478741255	None	None	N
P/M	0.6027	likely_pathogenic	0.5228	ambiguous	-0.279	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/N	0.824	likely_pathogenic	0.782	pathogenic	-0.719	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/Q	0.6153	likely_pathogenic	0.5625	ambiguous	-0.818	Destabilizing	1.0	D	0.866	deleterious	N	0.488113006	None	None	N
P/R	0.7507	likely_pathogenic	0.6853	pathogenic	-0.483	Destabilizing	1.0	D	0.907	deleterious	N	0.492885945	None	None	N
P/S	0.3341	likely_benign	0.3069	benign	-1.27	Destabilizing	1.0	D	0.835	deleterious	N	0.475821316	None	None	N
P/T	0.3081	likely_benign	0.2584	benign	-1.131	Destabilizing	1.0	D	0.824	deleterious	N	0.474021222	None	None	N
P/V	0.4417	ambiguous	0.3729	ambiguous	-0.587	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/W	0.9548	likely_pathogenic	0.933	pathogenic	-1.014	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
P/Y	0.8789	likely_pathogenic	0.8306	pathogenic	-0.677	Destabilizing	1.0	D	0.896	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.