TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3868	11827;11828;11829	chr2:178741631;178741630;178741629	chr2:179606358;179606357;179606356
N2AB	3551	10876;10877;10878	chr2:178741631;178741630;178741629	chr2:179606358;179606357;179606356
N2A	None	None	chr2:None	chr2:None
N2B	3505	10738;10739;10740	chr2:178741631;178741630;178741629	chr2:179606358;179606357;179606356
Novex-1	3630	11113;11114;11115	chr2:178741631;178741630;178741629	chr2:179606358;179606357;179606356
Novex-2	3697	11314;11315;11316	chr2:178741631;178741630;178741629	chr2:179606358;179606357;179606356
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-27
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.1652
• 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
F/C	None	None	0.997	D	0.575	0.544	None	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
F/L	rs727504700	None	0.002	N	0.091	0.194	None	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
F/A	0.796	likely_pathogenic	0.6836	pathogenic	-2.314	Highly Destabilizing	0.688	D	0.422	neutral	None	None	None	None	I
F/C	0.5853	likely_pathogenic	0.4435	ambiguous	-1.441	Destabilizing	0.997	D	0.575	neutral	D	0.640627355	None	None	I
F/D	0.9356	likely_pathogenic	0.8806	pathogenic	-1.526	Destabilizing	0.991	D	0.625	neutral	None	None	None	None	I
F/E	0.9257	likely_pathogenic	0.8749	pathogenic	-1.375	Destabilizing	0.974	D	0.629	neutral	None	None	None	None	I
F/G	0.9361	likely_pathogenic	0.8776	pathogenic	-2.701	Highly Destabilizing	0.915	D	0.61	neutral	None	None	None	None	I
F/H	0.8444	likely_pathogenic	0.763	pathogenic	-0.956	Destabilizing	0.998	D	0.535	neutral	None	None	None	None	I
F/I	0.2572	likely_benign	0.1943	benign	-1.111	Destabilizing	0.454	N	0.384	neutral	N	0.460033956	None	None	I
F/K	0.9446	likely_pathogenic	0.897	pathogenic	-1.651	Destabilizing	0.974	D	0.621	neutral	None	None	None	None	I
F/L	0.8722	likely_pathogenic	0.7608	pathogenic	-1.111	Destabilizing	0.002	N	0.091	neutral	N	0.467777208	None	None	I
F/M	0.5713	likely_pathogenic	0.4866	ambiguous	-0.862	Destabilizing	0.325	N	0.231	neutral	None	None	None	None	I
F/N	0.8358	likely_pathogenic	0.7486	pathogenic	-1.913	Destabilizing	0.991	D	0.624	neutral	None	None	None	None	I
F/P	0.9891	likely_pathogenic	0.9729	pathogenic	-1.512	Destabilizing	0.991	D	0.623	neutral	None	None	None	None	I
F/Q	0.9247	likely_pathogenic	0.8647	pathogenic	-1.877	Destabilizing	0.974	D	0.623	neutral	None	None	None	None	I
F/R	0.9039	likely_pathogenic	0.8246	pathogenic	-1.12	Destabilizing	0.974	D	0.63	neutral	None	None	None	None	I
F/S	0.7347	likely_pathogenic	0.6178	pathogenic	-2.68	Highly Destabilizing	0.891	D	0.542	neutral	N	0.509529631	None	None	I
F/T	0.6903	likely_pathogenic	0.5925	pathogenic	-2.423	Highly Destabilizing	0.915	D	0.521	neutral	None	None	None	None	I
F/V	0.3227	likely_benign	0.239	benign	-1.512	Destabilizing	0.454	N	0.359	neutral	N	0.477507199	None	None	I
F/W	0.6761	likely_pathogenic	0.5715	pathogenic	-0.19	Destabilizing	0.998	D	0.484	neutral	None	None	None	None	I
F/Y	0.252	likely_benign	0.2036	benign	-0.509	Destabilizing	0.891	D	0.451	neutral	N	0.478983276	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.