TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27025	81298;81299;81300	chr2:178565059;178565058;178565057	chr2:179429786;179429785;179429784
N2AB	25384	76375;76376;76377	chr2:178565059;178565058;178565057	chr2:179429786;179429785;179429784
N2A	24457	73594;73595;73596	chr2:178565059;178565058;178565057	chr2:179429786;179429785;179429784
N2B	17960	54103;54104;54105	chr2:178565059;178565058;178565057	chr2:179429786;179429785;179429784
Novex-1	18085	54478;54479;54480	chr2:178565059;178565058;178565057	chr2:179429786;179429785;179429784
Novex-2	18152	54679;54680;54681	chr2:178565059;178565058;178565057	chr2:179429786;179429785;179429784
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-84
• Domain position: 54
• Structural Position: 70
• Q(SASA): 0.4769
• 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
A/P	None	None	1.0	N	0.779	0.384	0.372087925617	gnomAD-4.0.0	1.59158E-06	None	None	None	None	I	None	0	0	None	4.76781E-05	0	None	0	0	0	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
A/C	0.6605	likely_pathogenic	0.679	pathogenic	-0.826	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
A/D	0.8255	likely_pathogenic	0.8327	pathogenic	-0.964	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
A/E	0.7162	likely_pathogenic	0.7443	pathogenic	-1.091	Destabilizing	1.0	D	0.779	deleterious	N	0.458971925	None	None	I
A/F	0.7163	likely_pathogenic	0.7551	pathogenic	-1.169	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
A/G	0.2098	likely_benign	0.2155	benign	-0.814	Destabilizing	1.0	D	0.543	neutral	N	0.458761281	None	None	I
A/H	0.8095	likely_pathogenic	0.822	pathogenic	-0.88	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
A/I	0.6117	likely_pathogenic	0.6488	pathogenic	-0.521	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
A/K	0.8427	likely_pathogenic	0.8688	pathogenic	-0.976	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
A/L	0.3675	ambiguous	0.4185	ambiguous	-0.521	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
A/M	0.4059	ambiguous	0.4467	ambiguous	-0.329	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
A/N	0.5004	ambiguous	0.5144	ambiguous	-0.617	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
A/P	0.5425	ambiguous	0.5228	ambiguous	-0.538	Destabilizing	1.0	D	0.779	deleterious	N	0.519001664	None	None	I
A/Q	0.5735	likely_pathogenic	0.6079	pathogenic	-0.925	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
A/R	0.7914	likely_pathogenic	0.8295	pathogenic	-0.467	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
A/S	0.1192	likely_benign	0.1143	benign	-0.866	Destabilizing	1.0	D	0.523	neutral	N	0.424032632	None	None	I
A/T	0.1524	likely_benign	0.1603	benign	-0.916	Destabilizing	1.0	D	0.686	prob.neutral	N	0.460684079	None	None	I
A/V	0.313	likely_benign	0.341	ambiguous	-0.538	Destabilizing	1.0	D	0.631	neutral	N	0.498735461	None	None	I
A/W	0.9453	likely_pathogenic	0.9602	pathogenic	-1.341	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
A/Y	0.8049	likely_pathogenic	0.8344	pathogenic	-0.992	Destabilizing	1.0	D	0.793	deleterious	None	None	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.