TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6373	19342;19343;19344	chr2:178728921;178728920;178728919	chr2:179593648;179593647;179593646
N2AB	6056	18391;18392;18393	chr2:178728921;178728920;178728919	chr2:179593648;179593647;179593646
N2A	5129	15610;15611;15612	chr2:178728921;178728920;178728919	chr2:179593648;179593647;179593646
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-47
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.2754
• 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/G	rs367868361	-1.371	0.959	N	0.503	0.264	None	gnomAD-2.1.1	2.16E-05	None	None	None	None	I	None	4.14E-05	0	None	0	0	None	0	None	0	3.94E-05	0
E/G	rs367868361	-1.371	0.959	N	0.503	0.264	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	4.41E-05	0	0
E/G	rs367868361	-1.371	0.959	N	0.503	0.264	None	gnomAD-4.0.0	7.39472E-05	None	None	None	None	I	None	1.33629E-05	0	None	0	0	None	0	0	9.8529E-05	0	3.21151E-05
E/K	rs1310419887	-0.361	0.979	N	0.395	0.33	0.339555952218	gnomAD-2.1.1	4.07E-06	None	None	None	None	I	None	0	0	None	0	5.59E-05	None	0	None	0	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	0.2516	likely_benign	0.254	benign	-0.795	Destabilizing	0.238	N	0.22	neutral	N	0.405668663	None	None	I
E/C	0.9451	likely_pathogenic	0.9431	pathogenic	-0.409	Destabilizing	1.0	D	0.549	neutral	None	None	None	None	I
E/D	0.2309	likely_benign	0.3247	benign	-1.106	Destabilizing	0.068	N	0.106	neutral	N	0.459580506	None	None	I
E/F	0.9214	likely_pathogenic	0.9252	pathogenic	-0.003	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	I
E/G	0.3563	ambiguous	0.3871	ambiguous	-1.21	Destabilizing	0.959	D	0.503	neutral	N	0.51770609	None	None	I
E/H	0.7641	likely_pathogenic	0.7968	pathogenic	-0.234	Destabilizing	0.999	D	0.455	neutral	None	None	None	None	I
E/I	0.6977	likely_pathogenic	0.7062	pathogenic	0.356	Stabilizing	0.991	D	0.601	neutral	None	None	None	None	I
E/K	0.4098	ambiguous	0.4569	ambiguous	-0.572	Destabilizing	0.979	D	0.395	neutral	N	0.474029883	None	None	I
E/L	0.7122	likely_pathogenic	0.7276	pathogenic	0.356	Stabilizing	0.969	D	0.575	neutral	None	None	None	None	I
E/M	0.7413	likely_pathogenic	0.7451	pathogenic	0.798	Stabilizing	1.0	D	0.534	neutral	None	None	None	None	I
E/N	0.5165	ambiguous	0.5973	pathogenic	-1.145	Destabilizing	0.969	D	0.442	neutral	None	None	None	None	I
E/P	0.9803	likely_pathogenic	0.9855	pathogenic	-0.007	Destabilizing	0.995	D	0.507	neutral	None	None	None	None	I
E/Q	0.2162	likely_benign	0.2239	benign	-0.968	Destabilizing	0.979	D	0.469	neutral	N	0.4090184	None	None	I
E/R	0.5608	ambiguous	0.5964	pathogenic	-0.251	Destabilizing	0.995	D	0.457	neutral	None	None	None	None	I
E/S	0.3202	likely_benign	0.3613	ambiguous	-1.527	Destabilizing	0.864	D	0.352	neutral	None	None	None	None	I
E/T	0.437	ambiguous	0.428	ambiguous	-1.173	Destabilizing	0.293	N	0.244	neutral	None	None	None	None	I
E/V	0.4195	ambiguous	0.4238	ambiguous	-0.007	Destabilizing	0.959	D	0.539	neutral	N	0.439415877	None	None	I
E/W	0.9791	likely_pathogenic	0.9818	pathogenic	0.285	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	I
E/Y	0.8823	likely_pathogenic	0.8917	pathogenic	0.283	Stabilizing	0.999	D	0.553	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.