TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20187	60784;60785;60786	chr2:178591166;178591165;178591164	chr2:179455893;179455892;179455891
N2AB	18546	55861;55862;55863	chr2:178591166;178591165;178591164	chr2:179455893;179455892;179455891
N2A	17619	53080;53081;53082	chr2:178591166;178591165;178591164	chr2:179455893;179455892;179455891
N2B	11122	33589;33590;33591	chr2:178591166;178591165;178591164	chr2:179455893;179455892;179455891
Novex-1	11247	33964;33965;33966	chr2:178591166;178591165;178591164	chr2:179455893;179455892;179455891
Novex-2	11314	34165;34166;34167	chr2:178591166;178591165;178591164	chr2:179455893;179455892;179455891
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: Fn3-34
• Domain position: 17
• Structural Position: 18
• Q(SASA): 0.4426
• 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/Q	rs2154184823	None	0.722	D	0.517	0.259	0.251639045875	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2411	likely_benign	0.2434	benign	-0.853	Destabilizing	0.722	D	0.506	neutral	N	0.496162089	None	None	I
E/C	0.8903	likely_pathogenic	0.8896	pathogenic	-0.492	Destabilizing	0.996	D	0.693	prob.neutral	None	None	None	None	I
E/D	0.0984	likely_benign	0.107	benign	-0.946	Destabilizing	0.001	N	0.097	neutral	N	0.38812776	None	None	I
E/F	0.8257	likely_pathogenic	0.8171	pathogenic	-0.497	Destabilizing	0.987	D	0.602	neutral	None	None	None	None	I
E/G	0.2056	likely_benign	0.2179	benign	-1.171	Destabilizing	0.722	D	0.488	neutral	N	0.495815373	None	None	I
E/H	0.5353	ambiguous	0.535	ambiguous	-0.787	Destabilizing	0.987	D	0.473	neutral	None	None	None	None	I
E/I	0.5676	likely_pathogenic	0.555	ambiguous	0.005	Stabilizing	0.961	D	0.599	neutral	None	None	None	None	I
E/K	0.2348	likely_benign	0.2256	benign	-0.916	Destabilizing	0.722	D	0.551	neutral	N	0.500221115	None	None	I
E/L	0.546	ambiguous	0.5299	ambiguous	0.005	Stabilizing	0.961	D	0.581	neutral	None	None	None	None	I
E/M	0.6032	likely_pathogenic	0.5973	pathogenic	0.408	Stabilizing	0.996	D	0.555	neutral	None	None	None	None	I
E/N	0.2588	likely_benign	0.2778	benign	-1.127	Destabilizing	0.633	D	0.515	neutral	None	None	None	None	I
E/P	0.9186	likely_pathogenic	0.9224	pathogenic	-0.261	Destabilizing	0.961	D	0.486	neutral	None	None	None	None	I
E/Q	0.1798	likely_benign	0.1747	benign	-1.003	Destabilizing	0.722	D	0.517	neutral	D	0.523097975	None	None	I
E/R	0.3575	ambiguous	0.3433	ambiguous	-0.62	Destabilizing	0.961	D	0.503	neutral	None	None	None	None	I
E/S	0.2223	likely_benign	0.233	benign	-1.417	Destabilizing	0.633	D	0.504	neutral	None	None	None	None	I
E/T	0.2603	likely_benign	0.2588	benign	-1.175	Destabilizing	0.775	D	0.494	neutral	None	None	None	None	I
E/V	0.3752	ambiguous	0.3655	ambiguous	-0.261	Destabilizing	0.949	D	0.501	neutral	N	0.478775071	None	None	I
E/W	0.899	likely_pathogenic	0.8988	pathogenic	-0.345	Destabilizing	0.996	D	0.699	prob.neutral	None	None	None	None	I
E/Y	0.6549	likely_pathogenic	0.6487	pathogenic	-0.322	Destabilizing	0.987	D	0.57	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.