TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31787	95584;95585;95586	chr2:178545877;178545876;178545875	chr2:179410604;179410603;179410602
N2AB	30146	90661;90662;90663	chr2:178545877;178545876;178545875	chr2:179410604;179410603;179410602
N2A	29219	87880;87881;87882	chr2:178545877;178545876;178545875	chr2:179410604;179410603;179410602
N2B	22722	68389;68390;68391	chr2:178545877;178545876;178545875	chr2:179410604;179410603;179410602
Novex-1	22847	68764;68765;68766	chr2:178545877;178545876;178545875	chr2:179410604;179410603;179410602
Novex-2	22914	68965;68966;68967	chr2:178545877;178545876;178545875	chr2:179410604;179410603;179410602
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-119
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.4876
• 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
K/N	rs1225133278	0.173	1.0	N	0.671	0.323	0.232513804876	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/N	rs1225133278	0.173	1.0	N	0.671	0.323	0.232513804876	gnomAD-4.0.0	2.0526E-06	None	None	None	None	I	None	0	2.23604E-05	None	0	0	None	0	0	1.79895E-06	0	0
K/T	None	None	1.0	N	0.621	0.553	0.364926071151	gnomAD-4.0.0	1.3684E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79895E-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
K/A	0.5612	ambiguous	0.5455	ambiguous	-0.171	Destabilizing	0.999	D	0.594	neutral	None	None	None	None	I
K/C	0.7901	likely_pathogenic	0.7368	pathogenic	-0.307	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
K/D	0.8115	likely_pathogenic	0.7941	pathogenic	0.044	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	I
K/E	0.4314	ambiguous	0.4184	ambiguous	0.075	Stabilizing	0.999	D	0.562	neutral	N	0.496180732	None	None	I
K/F	0.9245	likely_pathogenic	0.9066	pathogenic	-0.322	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	I
K/G	0.7372	likely_pathogenic	0.6975	pathogenic	-0.393	Destabilizing	1.0	D	0.577	neutral	None	None	None	None	I
K/H	0.4501	ambiguous	0.3883	ambiguous	-0.658	Destabilizing	1.0	D	0.585	neutral	None	None	None	None	I
K/I	0.5377	ambiguous	0.5173	ambiguous	0.344	Stabilizing	1.0	D	0.637	neutral	N	0.474446658	None	None	I
K/L	0.5832	likely_pathogenic	0.5622	ambiguous	0.344	Stabilizing	1.0	D	0.577	neutral	None	None	None	None	I
K/M	0.4465	ambiguous	0.4321	ambiguous	0.067	Stabilizing	1.0	D	0.583	neutral	None	None	None	None	I
K/N	0.7108	likely_pathogenic	0.6861	pathogenic	0.078	Stabilizing	1.0	D	0.671	neutral	N	0.481559774	None	None	I
K/P	0.7997	likely_pathogenic	0.7682	pathogenic	0.201	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	I
K/Q	0.2269	likely_benign	0.2134	benign	-0.035	Destabilizing	1.0	D	0.669	neutral	N	0.511611545	None	None	I
K/R	0.0936	likely_benign	0.0873	benign	-0.121	Destabilizing	0.999	D	0.484	neutral	N	0.467494444	None	None	I
K/S	0.6714	likely_pathogenic	0.635	pathogenic	-0.413	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	I
K/T	0.3401	ambiguous	0.3318	benign	-0.218	Destabilizing	1.0	D	0.621	neutral	N	0.47898888	None	None	I
K/V	0.5109	ambiguous	0.4843	ambiguous	0.201	Stabilizing	1.0	D	0.618	neutral	None	None	None	None	I
K/W	0.9002	likely_pathogenic	0.8705	pathogenic	-0.335	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	I
K/Y	0.819	likely_pathogenic	0.7783	pathogenic	0.006	Stabilizing	1.0	D	0.621	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.