TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26081	78466;78467;78468	chr2:178567891;178567890;178567889	chr2:179432618;179432617;179432616
N2AB	24440	73543;73544;73545	chr2:178567891;178567890;178567889	chr2:179432618;179432617;179432616
N2A	23513	70762;70763;70764	chr2:178567891;178567890;178567889	chr2:179432618;179432617;179432616
N2B	17016	51271;51272;51273	chr2:178567891;178567890;178567889	chr2:179432618;179432617;179432616
Novex-1	17141	51646;51647;51648	chr2:178567891;178567890;178567889	chr2:179432618;179432617;179432616
Novex-2	17208	51847;51848;51849	chr2:178567891;178567890;178567889	chr2:179432618;179432617;179432616
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-77
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.8117
• 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
E/D	rs768895653	0.021	0.997	N	0.537	0.11	0.104622674875	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
E/D	rs768895653	0.021	0.997	N	0.537	0.11	0.104622674875	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs768895653	0.021	0.997	N	0.537	0.11	0.104622674875	gnomAD-4.0.0	1.30155E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.6107E-05	0	3.20318E-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
E/A	0.2707	likely_benign	0.2992	benign	-0.339	Destabilizing	0.997	D	0.778	deleterious	N	0.458473137	None	None	I
E/C	0.9376	likely_pathogenic	0.9377	pathogenic	-0.298	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
E/D	0.1365	likely_benign	0.1214	benign	-0.303	Destabilizing	0.997	D	0.537	neutral	N	0.479853338	None	None	I
E/F	0.9073	likely_pathogenic	0.9234	pathogenic	-0.129	Destabilizing	1.0	D	0.671	prob.neutral	None	None	None	None	I
E/G	0.3544	ambiguous	0.3711	ambiguous	-0.519	Destabilizing	0.999	D	0.66	prob.neutral	N	0.467564944	None	None	I
E/H	0.7677	likely_pathogenic	0.7889	pathogenic	0.382	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
E/I	0.5755	likely_pathogenic	0.6107	pathogenic	0.1	Stabilizing	0.999	D	0.699	prob.delet.	None	None	None	None	I
E/K	0.3662	ambiguous	0.401	ambiguous	0.229	Stabilizing	0.997	D	0.681	prob.neutral	N	0.453068313	None	None	I
E/L	0.6529	likely_pathogenic	0.683	pathogenic	0.1	Stabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	I
E/M	0.7184	likely_pathogenic	0.7483	pathogenic	-0.011	Destabilizing	1.0	D	0.671	prob.neutral	None	None	None	None	I
E/N	0.4091	ambiguous	0.43	ambiguous	-0.137	Destabilizing	0.999	D	0.804	deleterious	None	None	None	None	I
E/P	0.5865	likely_pathogenic	0.6128	pathogenic	-0.028	Destabilizing	0.999	D	0.744	deleterious	None	None	None	None	I
E/Q	0.2913	likely_benign	0.3227	benign	-0.092	Destabilizing	0.999	D	0.694	prob.delet.	N	0.460728089	None	None	I
E/R	0.5719	likely_pathogenic	0.6094	pathogenic	0.578	Stabilizing	0.999	D	0.797	deleterious	None	None	None	None	I
E/S	0.3396	likely_benign	0.369	ambiguous	-0.306	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	I
E/T	0.4023	ambiguous	0.4427	ambiguous	-0.15	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	I
E/V	0.3881	ambiguous	0.429	ambiguous	-0.028	Destabilizing	0.999	D	0.691	prob.delet.	N	0.46426958	None	None	I
E/W	0.9795	likely_pathogenic	0.9818	pathogenic	0.039	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
E/Y	0.8511	likely_pathogenic	0.8664	pathogenic	0.118	Stabilizing	1.0	D	0.675	prob.neutral	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.