TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26009	78250;78251;78252	chr2:178568107;178568106;178568105	chr2:179432834;179432833;179432832
N2AB	24368	73327;73328;73329	chr2:178568107;178568106;178568105	chr2:179432834;179432833;179432832
N2A	23441	70546;70547;70548	chr2:178568107;178568106;178568105	chr2:179432834;179432833;179432832
N2B	16944	51055;51056;51057	chr2:178568107;178568106;178568105	chr2:179432834;179432833;179432832
Novex-1	17069	51430;51431;51432	chr2:178568107;178568106;178568105	chr2:179432834;179432833;179432832
Novex-2	17136	51631;51632;51633	chr2:178568107;178568106;178568105	chr2:179432834;179432833;179432832
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-77
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.0987
• 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/M	rs951099049	None	0.002	N	0.335	0.126	0.143124449307	gnomAD-4.0.0	1.59205E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02627E-05
I/T	rs1328584440	-2.59	0.012	N	0.557	0.362	0.648717662934	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/T	rs1328584440	-2.59	0.012	N	0.557	0.362	0.648717662934	gnomAD-4.0.0	4.10606E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39749E-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
I/A	0.901	likely_pathogenic	0.9339	pathogenic	-2.979	Highly Destabilizing	0.007	N	0.544	neutral	None	None	None	None	N
I/C	0.8909	likely_pathogenic	0.9125	pathogenic	-1.771	Destabilizing	0.356	N	0.729	prob.delet.	None	None	None	None	N
I/D	0.9987	likely_pathogenic	0.9993	pathogenic	-3.48	Highly Destabilizing	0.136	N	0.781	deleterious	None	None	None	None	N
I/E	0.9957	likely_pathogenic	0.9972	pathogenic	-3.167	Highly Destabilizing	0.136	N	0.746	deleterious	None	None	None	None	N
I/F	0.4691	ambiguous	0.4895	ambiguous	-1.756	Destabilizing	0.072	N	0.533	neutral	None	None	None	None	N
I/G	0.9849	likely_pathogenic	0.9911	pathogenic	-3.543	Highly Destabilizing	0.136	N	0.733	prob.delet.	None	None	None	None	N
I/H	0.9925	likely_pathogenic	0.9949	pathogenic	-3.146	Highly Destabilizing	0.628	D	0.832	deleterious	None	None	None	None	N
I/K	0.9936	likely_pathogenic	0.9957	pathogenic	-2.206	Highly Destabilizing	0.055	N	0.734	prob.delet.	N	0.513857945	None	None	N
I/L	0.1236	likely_benign	0.1426	benign	-1.255	Destabilizing	None	N	0.181	neutral	N	0.39704274	None	None	N
I/M	0.2505	likely_benign	0.3445	ambiguous	-1.351	Destabilizing	0.002	N	0.335	neutral	N	0.476800061	None	None	N
I/N	0.9786	likely_pathogenic	0.9871	pathogenic	-2.919	Highly Destabilizing	0.356	N	0.805	deleterious	None	None	None	None	N
I/P	0.9924	likely_pathogenic	0.9947	pathogenic	-1.825	Destabilizing	0.136	N	0.781	deleterious	None	None	None	None	N
I/Q	0.9897	likely_pathogenic	0.993	pathogenic	-2.56	Highly Destabilizing	0.356	N	0.8	deleterious	None	None	None	None	N
I/R	0.9897	likely_pathogenic	0.993	pathogenic	-2.247	Highly Destabilizing	0.295	N	0.793	deleterious	N	0.513857945	None	None	N
I/S	0.9637	likely_pathogenic	0.9754	pathogenic	-3.373	Highly Destabilizing	0.072	N	0.692	prob.neutral	None	None	None	None	N
I/T	0.8891	likely_pathogenic	0.931	pathogenic	-2.913	Highly Destabilizing	0.012	N	0.557	neutral	N	0.513857945	None	None	N
I/V	0.0926	likely_benign	0.1033	benign	-1.825	Destabilizing	None	N	0.155	neutral	N	0.415674147	None	None	N
I/W	0.9882	likely_pathogenic	0.9909	pathogenic	-2.068	Highly Destabilizing	0.864	D	0.829	deleterious	None	None	None	None	N
I/Y	0.9528	likely_pathogenic	0.96	pathogenic	-1.976	Destabilizing	0.136	N	0.687	prob.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.