TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20620	62083;62084;62085	chr2:178589867;178589866;178589865	chr2:179454594;179454593;179454592
N2AB	18979	57160;57161;57162	chr2:178589867;178589866;178589865	chr2:179454594;179454593;179454592
N2A	18052	54379;54380;54381	chr2:178589867;178589866;178589865	chr2:179454594;179454593;179454592
N2B	11555	34888;34889;34890	chr2:178589867;178589866;178589865	chr2:179454594;179454593;179454592
Novex-1	11680	35263;35264;35265	chr2:178589867;178589866;178589865	chr2:179454594;179454593;179454592
Novex-2	11747	35464;35465;35466	chr2:178589867;178589866;178589865	chr2:179454594;179454593;179454592
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-37
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1554
• 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
A/P	None	None	0.773	N	0.59	0.204	0.453962894745	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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
A/C	0.4542	ambiguous	0.397	ambiguous	-0.951	Destabilizing	0.944	D	0.58	neutral	None	None	None	None	N
A/D	0.6211	likely_pathogenic	0.597	pathogenic	-0.776	Destabilizing	0.388	N	0.576	neutral	None	None	None	None	N
A/E	0.6073	likely_pathogenic	0.5747	pathogenic	-0.797	Destabilizing	0.193	N	0.555	neutral	N	0.463281667	None	None	N
A/F	0.5772	likely_pathogenic	0.4677	ambiguous	-0.811	Destabilizing	0.818	D	0.594	neutral	None	None	None	None	N
A/G	0.1914	likely_benign	0.1952	benign	-0.99	Destabilizing	0.09	N	0.517	neutral	N	0.415125148	None	None	N
A/H	0.6743	likely_pathogenic	0.6223	pathogenic	-1.109	Destabilizing	0.944	D	0.533	neutral	None	None	None	None	N
A/I	0.5399	ambiguous	0.4748	ambiguous	-0.18	Destabilizing	0.69	D	0.59	neutral	None	None	None	None	N
A/K	0.7986	likely_pathogenic	0.771	pathogenic	-1.126	Destabilizing	0.241	N	0.553	neutral	None	None	None	None	N
A/L	0.3621	ambiguous	0.3013	benign	-0.18	Destabilizing	0.388	N	0.54	neutral	None	None	None	None	N
A/M	0.4251	ambiguous	0.3954	ambiguous	-0.264	Destabilizing	0.932	D	0.535	neutral	None	None	None	None	N
A/N	0.4636	ambiguous	0.4168	ambiguous	-0.931	Destabilizing	0.241	N	0.587	neutral	None	None	None	None	N
A/P	0.9392	likely_pathogenic	0.8877	pathogenic	-0.32	Destabilizing	0.773	D	0.59	neutral	N	0.475096171	None	None	N
A/Q	0.57	likely_pathogenic	0.5373	ambiguous	-1.027	Destabilizing	0.69	D	0.583	neutral	None	None	None	None	N
A/R	0.746	likely_pathogenic	0.699	pathogenic	-0.827	Destabilizing	0.69	D	0.587	neutral	None	None	None	None	N
A/S	0.095	likely_benign	0.0883	benign	-1.317	Destabilizing	None	N	0.178	neutral	N	0.350228307	None	None	N
A/T	0.11	likely_benign	0.1115	benign	-1.227	Destabilizing	0.006	N	0.199	neutral	N	0.409505897	None	None	N
A/V	0.276	likely_benign	0.2525	benign	-0.32	Destabilizing	0.324	N	0.532	neutral	N	0.454560609	None	None	N
A/W	0.9038	likely_pathogenic	0.846	pathogenic	-1.161	Destabilizing	0.981	D	0.606	neutral	None	None	None	None	N
A/Y	0.7097	likely_pathogenic	0.6076	pathogenic	-0.734	Destabilizing	0.818	D	0.575	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.