TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6334	19225;19226;19227	chr2:178729038;178729037;178729036	chr2:179593765;179593764;179593763
N2AB	6017	18274;18275;18276	chr2:178729038;178729037;178729036	chr2:179593765;179593764;179593763
N2A	5090	15493;15494;15495	chr2:178729038;178729037;178729036	chr2:179593765;179593764;179593763
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: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-47
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.7895
• 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/D	rs755041916	0.041	0.001	N	0.152	0.073	0.313210971179	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
E/D	rs755041916	0.041	0.001	N	0.152	0.073	0.313210971179	gnomAD-4.0.0	6.84613E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16063E-05	0
E/G	rs2079893948	None	0.193	N	0.344	0.277	0.49741755877	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-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	0.1201	likely_benign	0.1178	benign	-0.488	Destabilizing	0.09	N	0.321	neutral	N	0.511702837	None	None	I
E/C	0.7781	likely_pathogenic	0.7888	pathogenic	-0.211	Destabilizing	0.981	D	0.339	neutral	None	None	None	None	I
E/D	0.1325	likely_benign	0.138	benign	-0.528	Destabilizing	0.001	N	0.152	neutral	N	0.508086529	None	None	I
E/F	0.6729	likely_pathogenic	0.6966	pathogenic	-0.12	Destabilizing	0.932	D	0.319	neutral	None	None	None	None	I
E/G	0.1069	likely_benign	0.1034	benign	-0.74	Destabilizing	0.193	N	0.344	neutral	N	0.490229141	None	None	I
E/H	0.3791	ambiguous	0.3898	ambiguous	0.088	Stabilizing	0.818	D	0.259	neutral	None	None	None	None	I
E/I	0.3396	likely_benign	0.3473	ambiguous	0.162	Stabilizing	0.818	D	0.342	neutral	None	None	None	None	I
E/K	0.0805	likely_benign	0.0814	benign	0.196	Stabilizing	0.001	N	0.173	neutral	N	0.501621446	None	None	I
E/L	0.376	ambiguous	0.3861	ambiguous	0.162	Stabilizing	0.388	N	0.361	neutral	None	None	None	None	I
E/M	0.3934	ambiguous	0.4029	ambiguous	0.235	Stabilizing	0.981	D	0.309	neutral	None	None	None	None	I
E/N	0.205	likely_benign	0.2075	benign	-0.332	Destabilizing	0.002	N	0.176	neutral	None	None	None	None	I
E/P	0.4002	ambiguous	0.3876	ambiguous	-0.033	Destabilizing	0.818	D	0.317	neutral	None	None	None	None	I
E/Q	0.1217	likely_benign	0.1183	benign	-0.248	Destabilizing	0.006	N	0.183	neutral	D	0.531635392	None	None	I
E/R	0.1536	likely_benign	0.1569	benign	0.492	Stabilizing	0.241	N	0.263	neutral	None	None	None	None	I
E/S	0.1562	likely_benign	0.1596	benign	-0.483	Destabilizing	0.116	N	0.251	neutral	None	None	None	None	I
E/T	0.1687	likely_benign	0.1661	benign	-0.267	Destabilizing	0.388	N	0.319	neutral	None	None	None	None	I
E/V	0.2007	likely_benign	0.2065	benign	-0.033	Destabilizing	0.324	N	0.373	neutral	N	0.49310275	None	None	I
E/W	0.8278	likely_pathogenic	0.8368	pathogenic	0.112	Stabilizing	0.981	D	0.42	neutral	None	None	None	None	I
E/Y	0.5279	ambiguous	0.5476	ambiguous	0.144	Stabilizing	0.932	D	0.316	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.