TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27904	83935;83936;83937	chr2:178562422;178562421;178562420	chr2:179427149;179427148;179427147
N2AB	26263	79012;79013;79014	chr2:178562422;178562421;178562420	chr2:179427149;179427148;179427147
N2A	25336	76231;76232;76233	chr2:178562422;178562421;178562420	chr2:179427149;179427148;179427147
N2B	18839	56740;56741;56742	chr2:178562422;178562421;178562420	chr2:179427149;179427148;179427147
Novex-1	18964	57115;57116;57117	chr2:178562422;178562421;178562420	chr2:179427149;179427148;179427147
Novex-2	19031	57316;57317;57318	chr2:178562422;178562421;178562420	chr2:179427149;179427148;179427147
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-91
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.3144
• 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
T/A	rs1320086002	-0.98	0.045	N	0.296	0.093	0.139678290688	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	9.97E-05	0	None	0	None	0	0	0
T/A	rs1320086002	-0.98	0.045	N	0.296	0.093	0.139678290688	gnomAD-4.0.0	1.59303E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02627E-05
T/I	rs1704030695	None	0.62	N	0.384	0.174	0.245101548738	gnomAD-4.0.0	3.18637E-06	None	None	None	None	N	None	0	0	None	0	5.55772E-05	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
T/A	0.0726	likely_benign	0.0761	benign	-0.969	Destabilizing	0.045	N	0.296	neutral	N	0.41858674	None	None	N
T/C	0.3515	ambiguous	0.3802	ambiguous	-0.593	Destabilizing	0.996	D	0.413	neutral	None	None	None	None	N
T/D	0.4741	ambiguous	0.5255	ambiguous	-0.118	Destabilizing	0.481	N	0.401	neutral	None	None	None	None	N
T/E	0.3084	likely_benign	0.354	ambiguous	-0.107	Destabilizing	0.755	D	0.355	neutral	None	None	None	None	N
T/F	0.2722	likely_benign	0.3354	benign	-1.027	Destabilizing	0.976	D	0.502	neutral	None	None	None	None	N
T/G	0.1821	likely_benign	0.1926	benign	-1.234	Destabilizing	0.795	D	0.448	neutral	None	None	None	None	N
T/H	0.2494	likely_benign	0.2846	benign	-1.467	Destabilizing	0.997	D	0.456	neutral	None	None	None	None	N
T/I	0.1591	likely_benign	0.1942	benign	-0.348	Destabilizing	0.62	D	0.384	neutral	N	0.481848785	None	None	N
T/K	0.1605	likely_benign	0.1757	benign	-0.709	Destabilizing	0.812	D	0.345	neutral	None	None	None	None	N
T/L	0.0841	likely_benign	0.0949	benign	-0.348	Destabilizing	0.013	N	0.123	neutral	None	None	None	None	N
T/M	0.0755	likely_benign	0.0814	benign	-0.056	Destabilizing	0.938	D	0.438	neutral	None	None	None	None	N
T/N	0.1206	likely_benign	0.1365	benign	-0.647	Destabilizing	0.412	N	0.378	neutral	N	0.469052846	None	None	N
T/P	0.0736	likely_benign	0.0755	benign	-0.523	Destabilizing	0.001	N	0.111	neutral	N	0.41389021	None	None	N
T/Q	0.1833	likely_benign	0.1952	benign	-0.8	Destabilizing	0.935	D	0.445	neutral	None	None	None	None	N
T/R	0.1501	likely_benign	0.1676	benign	-0.498	Destabilizing	0.976	D	0.435	neutral	None	None	None	None	N
T/S	0.1102	likely_benign	0.1188	benign	-0.987	Destabilizing	0.003	N	0.101	neutral	N	0.404252006	None	None	N
T/V	0.1229	likely_benign	0.1418	benign	-0.523	Destabilizing	0.04	N	0.11	neutral	None	None	None	None	N
T/W	0.6028	likely_pathogenic	0.6586	pathogenic	-0.918	Destabilizing	0.999	D	0.51	neutral	None	None	None	None	N
T/Y	0.2995	likely_benign	0.3558	ambiguous	-0.699	Destabilizing	0.988	D	0.496	neutral	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.