TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31514	94765;94766;94767	chr2:178546888;178546887;178546886	chr2:179411615;179411614;179411613
N2AB	29873	89842;89843;89844	chr2:178546888;178546887;178546886	chr2:179411615;179411614;179411613
N2A	28946	87061;87062;87063	chr2:178546888;178546887;178546886	chr2:179411615;179411614;179411613
N2B	22449	67570;67571;67572	chr2:178546888;178546887;178546886	chr2:179411615;179411614;179411613
Novex-1	22574	67945;67946;67947	chr2:178546888;178546887;178546886	chr2:179411615;179411614;179411613
Novex-2	22641	68146;68147;68148	chr2:178546888;178546887;178546886	chr2:179411615;179411614;179411613
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-118
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.6862
• 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
E/Q	rs1697413804	None	1.0	N	0.663	0.269	0.346768085243	gnomAD-4.0.0	1.65961E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.9931E-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
E/A	0.2793	likely_benign	0.2343	benign	-0.633	Destabilizing	0.996	D	0.631	neutral	N	0.473584057	None	None	N
E/C	0.9072	likely_pathogenic	0.8828	pathogenic	-0.368	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.2436	likely_benign	0.2135	benign	-0.747	Destabilizing	0.998	D	0.549	neutral	N	0.467089597	None	None	N
E/F	0.8525	likely_pathogenic	0.8069	pathogenic	-0.122	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/G	0.5052	ambiguous	0.4413	ambiguous	-0.944	Destabilizing	0.999	D	0.68	prob.neutral	N	0.495905048	None	None	N
E/H	0.6247	likely_pathogenic	0.5476	ambiguous	-0.175	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/I	0.356	ambiguous	0.2939	benign	0.196	Stabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
E/K	0.2656	likely_benign	0.2235	benign	-0.259	Destabilizing	0.998	D	0.575	neutral	N	0.508723168	None	None	N
E/L	0.5064	ambiguous	0.4442	ambiguous	0.196	Stabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
E/M	0.5216	ambiguous	0.453	ambiguous	0.369	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/N	0.4486	ambiguous	0.3769	ambiguous	-0.721	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
E/P	0.9854	likely_pathogenic	0.9771	pathogenic	-0.059	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/Q	0.1802	likely_benign	0.1559	benign	-0.612	Destabilizing	1.0	D	0.663	neutral	N	0.519729596	None	None	N
E/R	0.3977	ambiguous	0.3431	ambiguous	0.063	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
E/S	0.3679	ambiguous	0.3027	benign	-0.947	Destabilizing	0.994	D	0.578	neutral	None	None	None	None	N
E/T	0.3092	likely_benign	0.2537	benign	-0.693	Destabilizing	0.813	D	0.451	neutral	None	None	None	None	N
E/V	0.1967	likely_benign	0.1675	benign	-0.059	Destabilizing	0.999	D	0.676	prob.neutral	N	0.484675659	None	None	N
E/W	0.9569	likely_pathogenic	0.9429	pathogenic	0.126	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/Y	0.7965	likely_pathogenic	0.7345	pathogenic	0.128	Stabilizing	1.0	D	0.769	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.