TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19712	59359;59360;59361	chr2:178592985;178592984;178592983	chr2:179457712;179457711;179457710
N2AB	18071	54436;54437;54438	chr2:178592985;178592984;178592983	chr2:179457712;179457711;179457710
N2A	17144	51655;51656;51657	chr2:178592985;178592984;178592983	chr2:179457712;179457711;179457710
N2B	10647	32164;32165;32166	chr2:178592985;178592984;178592983	chr2:179457712;179457711;179457710
Novex-1	10772	32539;32540;32541	chr2:178592985;178592984;178592983	chr2:179457712;179457711;179457710
Novex-2	10839	32740;32741;32742	chr2:178592985;178592984;178592983	chr2:179457712;179457711;179457710
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-31
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1748
• 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
I/F	rs547436872	-1.7	1.0	N	0.818	0.546	0.566919426312	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
I/F	rs547436872	-1.7	1.0	N	0.818	0.546	0.566919426312	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
I/F	rs547436872	-1.7	1.0	N	0.818	0.546	0.566919426312	gnomAD-4.0.0	8.05745E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.10203E-05	0	0
I/L	rs547436872	-1.081	0.993	N	0.413	0.346	0.529361283073	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/L	rs547436872	-1.081	0.993	N	0.413	0.346	0.529361283073	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
I/L	rs547436872	-1.081	0.993	N	0.413	0.346	0.529361283073	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
I/L	rs547436872	-1.081	0.993	N	0.413	0.346	0.529361283073	gnomAD-4.0.0	6.84302E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15953E-05	0
I/M	rs928532463	-0.927	1.0	D	0.803	0.47	0.467074840246	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
I/M	rs928532463	-0.927	1.0	D	0.803	0.47	0.467074840246	gnomAD-4.0.0	3.18356E-06	None	None	None	None	N	None	0	2.28728E-05	None	0	2.77562E-05	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
I/A	0.9799	likely_pathogenic	0.9773	pathogenic	-2.152	Highly Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
I/C	0.9746	likely_pathogenic	0.9744	pathogenic	-1.298	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
I/D	0.9955	likely_pathogenic	0.9946	pathogenic	-1.626	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
I/E	0.9915	likely_pathogenic	0.9899	pathogenic	-1.534	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
I/F	0.8003	likely_pathogenic	0.8224	pathogenic	-1.329	Destabilizing	1.0	D	0.818	deleterious	N	0.520422219	None	None	N
I/G	0.9937	likely_pathogenic	0.9925	pathogenic	-2.58	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
I/H	0.988	likely_pathogenic	0.9876	pathogenic	-1.71	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
I/K	0.9737	likely_pathogenic	0.9706	pathogenic	-1.532	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
I/L	0.3633	ambiguous	0.3747	ambiguous	-0.991	Destabilizing	0.993	D	0.413	neutral	N	0.512347837	None	None	N
I/M	0.5323	ambiguous	0.5381	ambiguous	-0.758	Destabilizing	1.0	D	0.803	deleterious	D	0.531350906	None	None	N
I/N	0.9307	likely_pathogenic	0.9186	pathogenic	-1.475	Destabilizing	1.0	D	0.879	deleterious	N	0.518375212	None	None	N
I/P	0.9535	likely_pathogenic	0.9485	pathogenic	-1.351	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
I/Q	0.9849	likely_pathogenic	0.9834	pathogenic	-1.55	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
I/R	0.9722	likely_pathogenic	0.9678	pathogenic	-0.978	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
I/S	0.9757	likely_pathogenic	0.9705	pathogenic	-2.201	Highly Destabilizing	1.0	D	0.868	deleterious	D	0.53818776	None	None	N
I/T	0.9599	likely_pathogenic	0.9545	pathogenic	-1.979	Destabilizing	1.0	D	0.843	deleterious	N	0.520083505	None	None	N
I/V	0.1746	likely_benign	0.179	benign	-1.351	Destabilizing	0.993	D	0.399	neutral	N	0.498551821	None	None	N
I/W	0.9923	likely_pathogenic	0.9934	pathogenic	-1.479	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
I/Y	0.9587	likely_pathogenic	0.9593	pathogenic	-1.261	Destabilizing	1.0	D	0.861	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.