TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25692	77299;77300;77301	chr2:178569058;178569057;178569056	chr2:179433785;179433784;179433783
N2AB	24051	72376;72377;72378	chr2:178569058;178569057;178569056	chr2:179433785;179433784;179433783
N2A	23124	69595;69596;69597	chr2:178569058;178569057;178569056	chr2:179433785;179433784;179433783
N2B	16627	50104;50105;50106	chr2:178569058;178569057;178569056	chr2:179433785;179433784;179433783
Novex-1	16752	50479;50480;50481	chr2:178569058;178569057;178569056	chr2:179433785;179433784;179433783
Novex-2	16819	50680;50681;50682	chr2:178569058;178569057;178569056	chr2:179433785;179433784;179433783
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-74
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.3226
• 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
P/A	None	None	0.603	N	0.411	0.217	0.152612264143	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
P/A	0.0704	likely_benign	0.0819	benign	-0.919	Destabilizing	0.603	D	0.411	neutral	N	0.465409534	None	None	N
P/C	0.5204	ambiguous	0.5901	pathogenic	-0.587	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
P/D	0.899	likely_pathogenic	0.9121	pathogenic	-0.278	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
P/E	0.7127	likely_pathogenic	0.7376	pathogenic	-0.335	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
P/F	0.7922	likely_pathogenic	0.8336	pathogenic	-0.834	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
P/G	0.4373	ambiguous	0.4848	ambiguous	-1.156	Destabilizing	0.993	D	0.773	deleterious	None	None	None	None	N
P/H	0.5391	ambiguous	0.589	pathogenic	-0.649	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/I	0.5377	ambiguous	0.5882	pathogenic	-0.407	Destabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
P/K	0.7689	likely_pathogenic	0.7995	pathogenic	-0.598	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
P/L	0.3446	ambiguous	0.3786	ambiguous	-0.407	Destabilizing	0.997	D	0.757	deleterious	N	0.482451012	None	None	N
P/M	0.5188	ambiguous	0.5678	pathogenic	-0.325	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/N	0.6758	likely_pathogenic	0.7132	pathogenic	-0.31	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
P/Q	0.4584	ambiguous	0.498	ambiguous	-0.505	Destabilizing	1.0	D	0.858	deleterious	N	0.504544966	None	None	N
P/R	0.5959	likely_pathogenic	0.6369	pathogenic	-0.115	Destabilizing	0.999	D	0.869	deleterious	N	0.4866942	None	None	N
P/S	0.1877	likely_benign	0.2261	benign	-0.823	Destabilizing	0.995	D	0.793	deleterious	N	0.499908897	None	None	N
P/T	0.2032	likely_benign	0.2418	benign	-0.767	Destabilizing	0.997	D	0.757	deleterious	N	0.492174702	None	None	N
P/V	0.3502	ambiguous	0.3975	ambiguous	-0.541	Destabilizing	0.998	D	0.714	prob.delet.	None	None	None	None	N
P/W	0.9214	likely_pathogenic	0.9368	pathogenic	-0.945	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/Y	0.7913	likely_pathogenic	0.8311	pathogenic	-0.641	Destabilizing	1.0	D	0.874	deleterious	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.