TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14882	44869;44870;44871	chr2:178624636;178624635;178624634	chr2:179489363;179489362;179489361
N2AB	13241	39946;39947;39948	chr2:178624636;178624635;178624634	chr2:179489363;179489362;179489361
N2A	12314	37165;37166;37167	chr2:178624636;178624635;178624634	chr2:179489363;179489362;179489361
N2B	5817	17674;17675;17676	chr2:178624636;178624635;178624634	chr2:179489363;179489362;179489361
Novex-1	5942	18049;18050;18051	chr2:178624636;178624635;178624634	chr2:179489363;179489362;179489361
Novex-2	6009	18250;18251;18252	chr2:178624636;178624635;178624634	chr2:179489363;179489362;179489361
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-100
• Domain position: 30
• Structural Position: 45
• Q(SASA): 0.975
• 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
K/T	rs988336748	None	0.684	N	0.507	0.311	0.36256342048	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.49E-05	0
K/T	rs988336748	None	0.684	N	0.507	0.311	0.36256342048	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/T	rs988336748	None	0.684	N	0.507	0.311	0.36256342048	gnomAD-4.0.0	2.48061E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39227E-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
K/A	0.2823	likely_benign	0.1886	benign	0.012	Stabilizing	0.373	N	0.453	neutral	None	None	None	None	N
K/C	0.8669	likely_pathogenic	0.7892	pathogenic	-0.412	Destabilizing	0.996	D	0.461	neutral	None	None	None	None	N
K/D	0.4262	ambiguous	0.3096	benign	-0.324	Destabilizing	0.009	N	0.241	neutral	None	None	None	None	N
K/E	0.1657	likely_benign	0.1046	benign	-0.342	Destabilizing	0.001	N	0.181	neutral	N	0.432368553	None	None	N
K/F	0.8578	likely_pathogenic	0.7865	pathogenic	-0.338	Destabilizing	0.984	D	0.471	neutral	None	None	None	None	N
K/G	0.522	ambiguous	0.381	ambiguous	-0.108	Destabilizing	0.742	D	0.495	neutral	None	None	None	None	N
K/H	0.41	ambiguous	0.3309	benign	-0.213	Destabilizing	0.953	D	0.507	neutral	None	None	None	None	N
K/I	0.3867	ambiguous	0.2986	benign	0.245	Stabilizing	0.953	D	0.492	neutral	None	None	None	None	N
K/L	0.4044	ambiguous	0.3031	benign	0.245	Stabilizing	0.742	D	0.534	neutral	None	None	None	None	N
K/M	0.2978	likely_benign	0.2148	benign	-0.091	Destabilizing	0.994	D	0.484	neutral	D	0.561232636	None	None	N
K/N	0.3537	ambiguous	0.2687	benign	0.041	Stabilizing	0.684	D	0.459	neutral	N	0.495984221	None	None	N
K/P	0.4244	ambiguous	0.301	benign	0.19	Stabilizing	0.009	N	0.261	neutral	None	None	None	None	N
K/Q	0.188	likely_benign	0.1349	benign	-0.113	Destabilizing	0.521	D	0.458	neutral	N	0.498737994	None	None	N
K/R	0.1187	likely_benign	0.1042	benign	-0.111	Destabilizing	0.684	D	0.457	neutral	N	0.500149132	None	None	N
K/S	0.3739	ambiguous	0.2722	benign	-0.312	Destabilizing	0.543	D	0.434	neutral	None	None	None	None	N
K/T	0.1606	likely_benign	0.1161	benign	-0.219	Destabilizing	0.684	D	0.507	neutral	N	0.495592617	None	None	N
K/V	0.3004	likely_benign	0.2246	benign	0.19	Stabilizing	0.854	D	0.525	neutral	None	None	None	None	N
K/W	0.8936	likely_pathogenic	0.8255	pathogenic	-0.443	Destabilizing	0.996	D	0.504	neutral	None	None	None	None	N
K/Y	0.7586	likely_pathogenic	0.686	pathogenic	-0.094	Destabilizing	0.984	D	0.491	neutral	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.