TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6512	19759;19760;19761	chr2:178728290;178728289;178728288	chr2:179593017;179593016;179593015
N2AB	6195	18808;18809;18810	chr2:178728290;178728289;178728288	chr2:179593017;179593016;179593015
N2A	5268	16027;16028;16029	chr2:178728290;178728289;178728288	chr2:179593017;179593016;179593015
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-49
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.3887
• 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	rs2079716781	None	0.103	N	0.419	0.173	0.208000267992	gnomAD-4.0.0	1.36892E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79935E-06	0	0
A/V	rs200902581	-0.27	0.046	N	0.283	0.262	0.21279746466	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.30822E-04	None	0	0	0
A/V	rs200902581	-0.27	0.046	N	0.283	0.262	0.21279746466	gnomAD-4.0.0	6.16005E-06	None	None	None	None	N	None	2.98954E-05	0	None	0	0	None	0	0	0	9.27773E-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	0.4824	ambiguous	0.5177	ambiguous	-0.768	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
A/D	0.6953	likely_pathogenic	0.7211	pathogenic	-1.023	Destabilizing	0.968	D	0.822	deleterious	N	0.50920125	None	None	N
A/E	0.549	ambiguous	0.5792	pathogenic	-1.086	Destabilizing	0.919	D	0.759	deleterious	None	None	None	None	N
A/F	0.3906	ambiguous	0.3736	ambiguous	-0.963	Destabilizing	0.988	D	0.844	deleterious	None	None	None	None	N
A/G	0.198	likely_benign	0.2103	benign	-0.97	Destabilizing	0.811	D	0.642	neutral	N	0.509027891	None	None	N
A/H	0.6786	likely_pathogenic	0.6867	pathogenic	-1.185	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
A/I	0.2861	likely_benign	0.2839	benign	-0.313	Destabilizing	0.851	D	0.713	prob.delet.	None	None	None	None	N
A/K	0.7079	likely_pathogenic	0.736	pathogenic	-1.145	Destabilizing	0.919	D	0.758	deleterious	None	None	None	None	N
A/L	0.2614	likely_benign	0.262	benign	-0.313	Destabilizing	0.702	D	0.697	prob.neutral	None	None	None	None	N
A/M	0.314	likely_benign	0.3145	benign	-0.259	Destabilizing	0.988	D	0.726	prob.delet.	None	None	None	None	N
A/N	0.5776	likely_pathogenic	0.5912	pathogenic	-0.758	Destabilizing	0.976	D	0.843	deleterious	None	None	None	None	N
A/P	0.3884	ambiguous	0.3907	ambiguous	-0.417	Destabilizing	0.984	D	0.759	deleterious	N	0.49044213	None	None	N
A/Q	0.574	likely_pathogenic	0.5897	pathogenic	-0.947	Destabilizing	0.988	D	0.742	deleterious	None	None	None	None	N
A/R	0.6251	likely_pathogenic	0.6468	pathogenic	-0.765	Destabilizing	0.976	D	0.745	deleterious	None	None	None	None	N
A/S	0.1176	likely_benign	0.1179	benign	-1.048	Destabilizing	0.103	N	0.419	neutral	N	0.479494418	None	None	N
A/T	0.1065	likely_benign	0.1098	benign	-1.02	Destabilizing	0.811	D	0.649	neutral	N	0.452654533	None	None	N
A/V	0.1362	likely_benign	0.1363	benign	-0.417	Destabilizing	0.046	N	0.283	neutral	N	0.302239572	None	None	N
A/W	0.8097	likely_pathogenic	0.8021	pathogenic	-1.271	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
A/Y	0.5557	ambiguous	0.5516	ambiguous	-0.885	Destabilizing	0.996	D	0.845	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.