TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19553	58882;58883;58884	chr2:178593643;178593642;178593641	chr2:179458370;179458369;179458368
N2AB	17912	53959;53960;53961	chr2:178593643;178593642;178593641	chr2:179458370;179458369;179458368
N2A	16985	51178;51179;51180	chr2:178593643;178593642;178593641	chr2:179458370;179458369;179458368
N2B	10488	31687;31688;31689	chr2:178593643;178593642;178593641	chr2:179458370;179458369;179458368
Novex-1	10613	32062;32063;32064	chr2:178593643;178593642;178593641	chr2:179458370;179458369;179458368
Novex-2	10680	32263;32264;32265	chr2:178593643;178593642;178593641	chr2:179458370;179458369;179458368
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGG
• RefSeq wild type template codon: GCC
• Domain: Fn3-29
• Domain position: 75
• Structural Position: 107
• Q(SASA): 0.1031
• 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
R/G	None	-2.172	0.922	D	0.591	0.47	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
R/G	None	-2.172	0.922	D	0.591	0.47	None	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
R/G	None	-2.172	0.922	D	0.591	0.47	None	gnomAD-4.0.0	3.10014E-06	None	None	None	None	N	None	1.33618E-05	0	None	0	0	None	0	0	3.39115E-06	0	0
R/P	None	None	0.988	D	0.68	0.522	0.614679400128	gnomAD-4.0.0	3.42273E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49817E-06	0	0
R/Q	rs543279513	-1.068	0.447	N	0.475	0.314	None	gnomAD-2.1.1	1.08E-05	None	None	None	None	N	None	1.24152E-04	0	None	0	0	None	0	None	0	0	0
R/Q	rs543279513	-1.068	0.447	N	0.475	0.314	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
R/Q	rs543279513	-1.068	0.447	N	0.475	0.314	None	1000 genomes	3.99361E-04	None	None	None	None	N	None	1.5E-03	0	None	None	0	0	None	None	None	0	None
R/Q	rs543279513	-1.068	0.447	N	0.475	0.314	None	gnomAD-4.0.0	7.43962E-06	None	None	None	None	N	None	5.33305E-05	0	None	0	0	None	0	0	5.93453E-06	1.09847E-05	0
R/W	rs372959465	-0.666	1.0	D	0.729	0.526	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	8.28E-05	0	None	0	5.2E-05	None	0	None	0	7.85E-06	0
R/W	rs372959465	-0.666	1.0	D	0.729	0.526	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	1.47E-05	0	0
R/W	rs372959465	-0.666	1.0	D	0.729	0.526	None	gnomAD-4.0.0	1.30206E-05	None	None	None	None	N	None	4.00855E-05	0	None	0	2.24024E-05	None	0	0	1.35646E-05	1.09837E-05	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
R/A	0.9432	likely_pathogenic	0.9351	pathogenic	-1.666	Destabilizing	0.754	D	0.572	neutral	None	None	None	None	N
R/C	0.4091	ambiguous	0.354	ambiguous	-1.621	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
R/D	0.9935	likely_pathogenic	0.9915	pathogenic	-1.066	Destabilizing	0.956	D	0.612	neutral	None	None	None	None	N
R/E	0.914	likely_pathogenic	0.8992	pathogenic	-0.831	Destabilizing	0.754	D	0.606	neutral	None	None	None	None	N
R/F	0.9733	likely_pathogenic	0.9627	pathogenic	-0.677	Destabilizing	0.993	D	0.783	deleterious	None	None	None	None	N
R/G	0.9321	likely_pathogenic	0.9147	pathogenic	-2.044	Highly Destabilizing	0.922	D	0.591	neutral	D	0.535221565	None	None	N
R/H	0.3763	ambiguous	0.3224	benign	-1.712	Destabilizing	0.978	D	0.617	neutral	None	None	None	None	N
R/I	0.8569	likely_pathogenic	0.8214	pathogenic	-0.569	Destabilizing	0.978	D	0.767	deleterious	None	None	None	None	N
R/K	0.4388	ambiguous	0.3786	ambiguous	-1.122	Destabilizing	0.559	D	0.647	neutral	None	None	None	None	N
R/L	0.8214	likely_pathogenic	0.7868	pathogenic	-0.569	Destabilizing	0.922	D	0.591	neutral	D	0.524118749	None	None	N
R/M	0.8886	likely_pathogenic	0.858	pathogenic	-1.093	Destabilizing	0.994	D	0.653	neutral	None	None	None	None	N
R/N	0.973	likely_pathogenic	0.9645	pathogenic	-1.401	Destabilizing	0.956	D	0.561	neutral	None	None	None	None	N
R/P	0.9983	likely_pathogenic	0.9982	pathogenic	-0.923	Destabilizing	0.988	D	0.68	prob.neutral	D	0.547084849	None	None	N
R/Q	0.3011	likely_benign	0.2679	benign	-1.157	Destabilizing	0.447	N	0.475	neutral	N	0.502416415	None	None	N
R/S	0.9562	likely_pathogenic	0.9444	pathogenic	-2.15	Highly Destabilizing	0.754	D	0.559	neutral	None	None	None	None	N
R/T	0.9219	likely_pathogenic	0.9009	pathogenic	-1.695	Destabilizing	0.956	D	0.551	neutral	None	None	None	None	N
R/V	0.888	likely_pathogenic	0.8592	pathogenic	-0.923	Destabilizing	0.956	D	0.73	prob.delet.	None	None	None	None	N
R/W	0.737	likely_pathogenic	0.6937	pathogenic	-0.26	Destabilizing	1.0	D	0.729	prob.delet.	D	0.54683136	None	None	N
R/Y	0.9123	likely_pathogenic	0.8806	pathogenic	-0.128	Destabilizing	0.978	D	0.72	prob.delet.	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.