TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21071	63436;63437;63438	chr2:178588196;178588195;178588194	chr2:179452923;179452922;179452921
N2AB	19430	58513;58514;58515	chr2:178588196;178588195;178588194	chr2:179452923;179452922;179452921
N2A	18503	55732;55733;55734	chr2:178588196;178588195;178588194	chr2:179452923;179452922;179452921
N2B	12006	36241;36242;36243	chr2:178588196;178588195;178588194	chr2:179452923;179452922;179452921
Novex-1	12131	36616;36617;36618	chr2:178588196;178588195;178588194	chr2:179452923;179452922;179452921
Novex-2	12198	36817;36818;36819	chr2:178588196;178588195;178588194	chr2:179452923;179452922;179452921
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-41
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1201
• 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
F/L	None	None	None	N	0.209	0.049	0.130388298395	gnomAD-4.0.0	1.67094E-06	None	None	None	None	N	None	0	0	None	0	2.82582E-05	None	0	0	0	0	0
F/Y	rs2154182814	None	0.106	N	0.574	0.183	0.370424759081	gnomAD-4.0.0	1.66884E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.15278E-05

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
F/A	0.5997	likely_pathogenic	0.5386	ambiguous	-2.661	Highly Destabilizing	0.031	N	0.573	neutral	None	None	None	None	N
F/C	0.3193	likely_benign	0.2619	benign	-1.43	Destabilizing	0.56	D	0.709	prob.delet.	N	0.461742872	None	None	N
F/D	0.9666	likely_pathogenic	0.9661	pathogenic	-3.463	Highly Destabilizing	0.628	D	0.743	deleterious	None	None	None	None	N
F/E	0.9681	likely_pathogenic	0.9675	pathogenic	-3.236	Highly Destabilizing	0.356	N	0.749	deleterious	None	None	None	None	N
F/G	0.8485	likely_pathogenic	0.827	pathogenic	-3.108	Highly Destabilizing	0.136	N	0.704	prob.neutral	None	None	None	None	N
F/H	0.9044	likely_pathogenic	0.8985	pathogenic	-1.874	Destabilizing	0.628	D	0.695	prob.neutral	None	None	None	None	N
F/I	0.1415	likely_benign	0.1167	benign	-1.187	Destabilizing	0.012	N	0.489	neutral	N	0.390706706	None	None	N
F/K	0.9595	likely_pathogenic	0.9616	pathogenic	-1.982	Destabilizing	0.136	N	0.714	prob.delet.	None	None	None	None	N
F/L	0.2123	likely_benign	0.1896	benign	-1.187	Destabilizing	None	N	0.209	neutral	N	0.301769851	None	None	N
F/M	0.2973	likely_benign	0.2538	benign	-0.878	Destabilizing	0.12	N	0.72	prob.delet.	None	None	None	None	N
F/N	0.9223	likely_pathogenic	0.9116	pathogenic	-2.584	Highly Destabilizing	0.628	D	0.753	deleterious	None	None	None	None	N
F/P	0.543	ambiguous	0.4487	ambiguous	-1.692	Destabilizing	0.628	D	0.755	deleterious	None	None	None	None	N
F/Q	0.9367	likely_pathogenic	0.9285	pathogenic	-2.471	Highly Destabilizing	0.628	D	0.757	deleterious	None	None	None	None	N
F/R	0.9182	likely_pathogenic	0.9145	pathogenic	-1.675	Destabilizing	0.356	N	0.745	deleterious	None	None	None	None	N
F/S	0.8425	likely_pathogenic	0.8161	pathogenic	-3.074	Highly Destabilizing	0.106	N	0.644	neutral	N	0.472439868	None	None	N
F/T	0.7225	likely_pathogenic	0.6658	pathogenic	-2.732	Highly Destabilizing	0.072	N	0.617	neutral	None	None	None	None	N
F/V	0.1515	likely_benign	0.1237	benign	-1.692	Destabilizing	0.005	N	0.544	neutral	N	0.343064687	None	None	N
F/W	0.718	likely_pathogenic	0.7241	pathogenic	-0.276	Destabilizing	0.864	D	0.613	neutral	None	None	None	None	N
F/Y	0.4108	ambiguous	0.4528	ambiguous	-0.672	Destabilizing	0.106	N	0.574	neutral	N	0.491198987	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.