TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32518	97777;97778;97779	chr2:178541525;178541524;178541523	chr2:179406252;179406251;179406250
N2AB	30877	92854;92855;92856	chr2:178541525;178541524;178541523	chr2:179406252;179406251;179406250
N2A	29950	90073;90074;90075	chr2:178541525;178541524;178541523	chr2:179406252;179406251;179406250
N2B	23453	70582;70583;70584	chr2:178541525;178541524;178541523	chr2:179406252;179406251;179406250
Novex-1	23578	70957;70958;70959	chr2:178541525;178541524;178541523	chr2:179406252;179406251;179406250
Novex-2	23645	71158;71159;71160	chr2:178541525;178541524;178541523	chr2:179406252;179406251;179406250
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-125
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.128
• 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
L/V	rs1178885715	-1.722	0.17	N	0.367	0.128	0.465975295344	gnomAD-2.1.1	7.17E-06	None	None	None	None	N	None	4.15E-05	0	None	0	0	None	0	None	0	7.85E-06	0
L/V	rs1178885715	-1.722	0.17	N	0.367	0.128	0.465975295344	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
L/V	rs1178885715	-1.722	0.17	N	0.367	0.128	0.465975295344	gnomAD-4.0.0	6.19966E-06	None	None	None	None	N	None	1.33522E-05	0	None	0	0	None	0	0	7.6308E-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
L/A	0.779	likely_pathogenic	0.7282	pathogenic	-2.65	Highly Destabilizing	0.953	D	0.675	neutral	None	None	None	None	N
L/C	0.7505	likely_pathogenic	0.7319	pathogenic	-1.586	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
L/D	0.9975	likely_pathogenic	0.9973	pathogenic	-3.359	Highly Destabilizing	0.998	D	0.911	deleterious	None	None	None	None	N
L/E	0.9797	likely_pathogenic	0.9765	pathogenic	-3.053	Highly Destabilizing	0.998	D	0.906	deleterious	None	None	None	None	N
L/F	0.5093	ambiguous	0.4966	ambiguous	-1.597	Destabilizing	0.982	D	0.692	prob.neutral	D	0.526318612	None	None	N
L/G	0.9679	likely_pathogenic	0.9611	pathogenic	-3.222	Highly Destabilizing	0.998	D	0.901	deleterious	None	None	None	None	N
L/H	0.9595	likely_pathogenic	0.9549	pathogenic	-2.948	Highly Destabilizing	0.999	D	0.872	deleterious	D	0.554084105	None	None	N
L/I	0.0909	likely_benign	0.0917	benign	-0.926	Destabilizing	0.046	N	0.353	neutral	D	0.525279849	None	None	N
L/K	0.9736	likely_pathogenic	0.9741	pathogenic	-1.987	Destabilizing	0.993	D	0.877	deleterious	None	None	None	None	N
L/M	0.1729	likely_benign	0.1679	benign	-0.972	Destabilizing	0.986	D	0.669	neutral	None	None	None	None	N
L/N	0.9793	likely_pathogenic	0.9777	pathogenic	-2.652	Highly Destabilizing	0.998	D	0.913	deleterious	None	None	None	None	N
L/P	0.9911	likely_pathogenic	0.9899	pathogenic	-1.492	Destabilizing	0.997	D	0.91	deleterious	D	0.554084105	None	None	N
L/Q	0.9265	likely_pathogenic	0.9151	pathogenic	-2.328	Highly Destabilizing	0.998	D	0.902	deleterious	None	None	None	None	N
L/R	0.9592	likely_pathogenic	0.9537	pathogenic	-2.006	Highly Destabilizing	0.997	D	0.897	deleterious	D	0.554084105	None	None	N
L/S	0.955	likely_pathogenic	0.9437	pathogenic	-3.152	Highly Destabilizing	0.993	D	0.869	deleterious	None	None	None	None	N
L/T	0.8527	likely_pathogenic	0.8223	pathogenic	-2.699	Highly Destabilizing	0.986	D	0.733	prob.delet.	None	None	None	None	N
L/V	0.104	likely_benign	0.0903	benign	-1.492	Destabilizing	0.17	N	0.367	neutral	N	0.489374977	None	None	N
L/W	0.9412	likely_pathogenic	0.9338	pathogenic	-2.054	Highly Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
L/Y	0.9212	likely_pathogenic	0.9201	pathogenic	-1.813	Destabilizing	0.998	D	0.754	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.