TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8661	26206;26207;26208	chr2:178715205;178715204;178715203	chr2:179579932;179579931;179579930
N2AB	8344	25255;25256;25257	chr2:178715205;178715204;178715203	chr2:179579932;179579931;179579930
N2A	7417	22474;22475;22476	chr2:178715205;178715204;178715203	chr2:179579932;179579931;179579930
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: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-72
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.3918
• 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
H/Y	None	None	0.846	N	0.419	0.138	0.209622950755	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	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
H/A	0.2741	likely_benign	0.2569	benign	-0.049	Destabilizing	0.16	N	0.406	neutral	None	None	None	None	N
H/C	0.2001	likely_benign	0.1954	benign	0.622	Stabilizing	0.981	D	0.487	neutral	None	None	None	None	N
H/D	0.2817	likely_benign	0.2512	benign	-0.2	Destabilizing	0.165	N	0.435	neutral	N	0.446434197	None	None	N
H/E	0.3235	likely_benign	0.3018	benign	-0.137	Destabilizing	0.153	N	0.362	neutral	None	None	None	None	N
H/F	0.27	likely_benign	0.248	benign	0.899	Stabilizing	0.893	D	0.529	neutral	None	None	None	None	N
H/G	0.3677	ambiguous	0.3512	ambiguous	-0.391	Destabilizing	0.003	N	0.425	neutral	None	None	None	None	N
H/I	0.2302	likely_benign	0.1973	benign	0.859	Stabilizing	0.457	N	0.532	neutral	None	None	None	None	N
H/K	0.2577	likely_benign	0.2662	benign	-0.04	Destabilizing	0.148	N	0.428	neutral	None	None	None	None	N
H/L	0.1075	likely_benign	0.1007	benign	0.859	Stabilizing	0.116	N	0.432	neutral	N	0.412993627	None	None	N
H/M	0.3987	ambiguous	0.3846	ambiguous	0.645	Stabilizing	0.948	D	0.481	neutral	None	None	None	None	N
H/N	0.1111	likely_benign	0.1064	benign	-0.051	Destabilizing	0.165	N	0.418	neutral	N	0.468540266	None	None	N
H/P	0.3547	ambiguous	0.3189	benign	0.581	Stabilizing	0.493	N	0.496	neutral	N	0.465046957	None	None	N
H/Q	0.1655	likely_benign	0.1675	benign	0.136	Stabilizing	0.025	N	0.289	neutral	N	0.444471328	None	None	N
H/R	0.1023	likely_benign	0.1098	benign	-0.722	Destabilizing	0.388	N	0.397	neutral	N	0.438582718	None	None	N
H/S	0.1927	likely_benign	0.1873	benign	0.051	Stabilizing	0.004	N	0.285	neutral	None	None	None	None	N
H/T	0.22	likely_benign	0.2147	benign	0.219	Stabilizing	0.004	N	0.412	neutral	None	None	None	None	N
H/V	0.1964	likely_benign	0.1774	benign	0.581	Stabilizing	0.305	N	0.461	neutral	None	None	None	None	N
H/W	0.3987	ambiguous	0.3847	ambiguous	1.01	Stabilizing	0.996	D	0.498	neutral	None	None	None	None	N
H/Y	0.0926	likely_benign	0.0838	benign	1.207	Stabilizing	0.846	D	0.419	neutral	N	0.466558753	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.