TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22274	67045;67046;67047	chr2:178580559;178580558;178580557	chr2:179445286;179445285;179445284
N2AB	20633	62122;62123;62124	chr2:178580559;178580558;178580557	chr2:179445286;179445285;179445284
N2A	19706	59341;59342;59343	chr2:178580559;178580558;178580557	chr2:179445286;179445285;179445284
N2B	13209	39850;39851;39852	chr2:178580559;178580558;178580557	chr2:179445286;179445285;179445284
Novex-1	13334	40225;40226;40227	chr2:178580559;178580558;178580557	chr2:179445286;179445285;179445284
Novex-2	13401	40426;40427;40428	chr2:178580559;178580558;178580557	chr2:179445286;179445285;179445284
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Ig-126
• Domain position: 10
• Structural Position: 18
• Q(SASA): 0.7862
• 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
R/C	rs770627108	-0.547	1.0	N	0.771	0.572	0.637424115254	gnomAD-2.1.1	8.11E-06	None	None	None	None	I	None	0	2.92E-05	None	0	0	None	0	None	0	8.97E-06	0
R/C	rs770627108	-0.547	1.0	N	0.771	0.572	0.637424115254	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	6.56E-05	0	0	0	None	0	0	1.47E-05	0	0
R/C	rs770627108	-0.547	1.0	N	0.771	0.572	0.637424115254	gnomAD-4.0.0	2.35703E-05	None	None	None	None	I	None	0	3.34113E-05	None	0	2.24075E-05	None	0	0	2.79865E-05	1.10057E-05	1.60308E-05
R/H	None	-0.748	1.0	N	0.734	0.436	0.518092603711	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	3.28E-05	None	0	1.79E-05	0
R/H	None	-0.748	1.0	N	0.734	0.436	0.518092603711	gnomAD-4.0.0	9.58641E-06	None	None	None	None	I	None	2.99258E-05	2.23964E-05	None	0	7.59955E-05	None	0	0	7.19907E-06	1.16074E-05	0
R/L	rs772979195	0.342	1.0	N	0.686	0.434	0.590198699859	gnomAD-2.1.1	1.62E-05	None	None	None	None	I	None	1.94376E-04	0	None	0	0	None	0	None	0	8.96E-06	0
R/L	rs772979195	0.342	1.0	N	0.686	0.434	0.590198699859	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/L	rs772979195	0.342	1.0	N	0.686	0.434	0.590198699859	gnomAD-4.0.0	2.48069E-06	None	None	None	None	I	None	4.0078E-05	0	None	0	0	None	0	0	8.48011E-07	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
R/A	0.9321	likely_pathogenic	0.9567	pathogenic	0.044	Stabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	I
R/C	0.6456	likely_pathogenic	0.7566	pathogenic	-0.213	Destabilizing	1.0	D	0.771	deleterious	N	0.521144506	None	None	I
R/D	0.9726	likely_pathogenic	0.9812	pathogenic	-0.147	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
R/E	0.8593	likely_pathogenic	0.9006	pathogenic	-0.076	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	I
R/F	0.9409	likely_pathogenic	0.9654	pathogenic	-0.166	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
R/G	0.8905	likely_pathogenic	0.929	pathogenic	-0.148	Destabilizing	1.0	D	0.686	prob.neutral	N	0.501937387	None	None	I
R/H	0.2949	likely_benign	0.3737	ambiguous	-0.647	Destabilizing	1.0	D	0.734	prob.delet.	N	0.494050575	None	None	I
R/I	0.882	likely_pathogenic	0.9277	pathogenic	0.514	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
R/K	0.2375	likely_benign	0.2903	benign	-0.077	Destabilizing	0.998	D	0.613	neutral	None	None	None	None	I
R/L	0.7664	likely_pathogenic	0.8355	pathogenic	0.514	Stabilizing	1.0	D	0.686	prob.neutral	N	0.513606992	None	None	I
R/M	0.8144	likely_pathogenic	0.8905	pathogenic	-0.016	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
R/N	0.9437	likely_pathogenic	0.965	pathogenic	0.025	Stabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
R/P	0.8908	likely_pathogenic	0.9243	pathogenic	0.378	Stabilizing	1.0	D	0.727	prob.delet.	D	0.535579774	None	None	I
R/Q	0.3342	likely_benign	0.4194	ambiguous	-0.013	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
R/S	0.956	likely_pathogenic	0.9707	pathogenic	-0.251	Destabilizing	1.0	D	0.699	prob.neutral	D	0.532459324	None	None	I
R/T	0.8743	likely_pathogenic	0.9203	pathogenic	-0.047	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
R/V	0.8915	likely_pathogenic	0.9312	pathogenic	0.378	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
R/W	0.6247	likely_pathogenic	0.7202	pathogenic	-0.27	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
R/Y	0.8461	likely_pathogenic	0.9023	pathogenic	0.144	Stabilizing	1.0	D	0.745	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.