TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9212	27859;27860;27861	chr2:178712196;178712195;178712194	chr2:179576923;179576922;179576921
N2AB	8895	26908;26909;26910	chr2:178712196;178712195;178712194	chr2:179576923;179576922;179576921
N2A	7968	24127;24128;24129	chr2:178712196;178712195;178712194	chr2:179576923;179576922;179576921
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-78
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.5096
• 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
E/K	rs769421279	0.297	0.822	N	0.439	0.303	0.366466682447	gnomAD-2.1.1	7.15E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.57E-05	0
E/K	rs769421279	0.297	0.822	N	0.439	0.303	0.366466682447	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs769421279	0.297	0.822	N	0.439	0.303	0.366466682447	gnomAD-4.0.0	3.84493E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.18195E-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	0.1345	likely_benign	0.1476	benign	-0.247	Destabilizing	0.014	N	0.292	neutral	N	0.485225484	None	None	I
E/C	0.808	likely_pathogenic	0.8494	pathogenic	-0.214	Destabilizing	0.994	D	0.619	neutral	None	None	None	None	I
E/D	0.1223	likely_benign	0.1364	benign	-0.33	Destabilizing	0.014	N	0.295	neutral	N	0.516031221	None	None	I
E/F	0.6537	likely_pathogenic	0.7102	pathogenic	-0.05	Destabilizing	0.978	D	0.628	neutral	None	None	None	None	I
E/G	0.1353	likely_benign	0.1553	benign	-0.445	Destabilizing	0.698	D	0.479	neutral	N	0.485251937	None	None	I
E/H	0.3807	ambiguous	0.4305	ambiguous	0.331	Stabilizing	0.998	D	0.453	neutral	None	None	None	None	I
E/I	0.2864	likely_benign	0.3292	benign	0.24	Stabilizing	0.956	D	0.628	neutral	None	None	None	None	I
E/K	0.124	likely_benign	0.1438	benign	0.262	Stabilizing	0.822	D	0.439	neutral	N	0.5061768	None	None	I
E/L	0.2631	likely_benign	0.3056	benign	0.24	Stabilizing	0.915	D	0.563	neutral	None	None	None	None	I
E/M	0.3792	ambiguous	0.4222	ambiguous	0.11	Stabilizing	0.998	D	0.549	neutral	None	None	None	None	I
E/N	0.2174	likely_benign	0.256	benign	-0.079	Destabilizing	0.956	D	0.431	neutral	None	None	None	None	I
E/P	0.5189	ambiguous	0.5912	pathogenic	0.098	Stabilizing	0.978	D	0.519	neutral	None	None	None	None	I
E/Q	0.103	likely_benign	0.11	benign	-0.032	Destabilizing	0.971	D	0.431	neutral	N	0.509507894	None	None	I
E/R	0.2308	likely_benign	0.2611	benign	0.569	Stabilizing	0.956	D	0.464	neutral	None	None	None	None	I
E/S	0.1726	likely_benign	0.1946	benign	-0.242	Destabilizing	0.754	D	0.401	neutral	None	None	None	None	I
E/T	0.1926	likely_benign	0.2139	benign	-0.079	Destabilizing	0.86	D	0.464	neutral	None	None	None	None	I
E/V	0.1672	likely_benign	0.1856	benign	0.098	Stabilizing	0.89	D	0.469	neutral	N	0.489113051	None	None	I
E/W	0.8644	likely_pathogenic	0.8927	pathogenic	0.095	Stabilizing	0.998	D	0.633	neutral	None	None	None	None	I
E/Y	0.5177	ambiguous	0.5774	pathogenic	0.192	Stabilizing	0.993	D	0.57	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.