TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26124	78595;78596;78597	chr2:178567762;178567761;178567760	chr2:179432489;179432488;179432487
N2AB	24483	73672;73673;73674	chr2:178567762;178567761;178567760	chr2:179432489;179432488;179432487
N2A	23556	70891;70892;70893	chr2:178567762;178567761;178567760	chr2:179432489;179432488;179432487
N2B	17059	51400;51401;51402	chr2:178567762;178567761;178567760	chr2:179432489;179432488;179432487
Novex-1	17184	51775;51776;51777	chr2:178567762;178567761;178567760	chr2:179432489;179432488;179432487
Novex-2	17251	51976;51977;51978	chr2:178567762;178567761;178567760	chr2:179432489;179432488;179432487
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: Fn3-78
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.0818
• 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/L	None	None	0.437	D	0.461	0.174	0.474954162714	gnomAD-4.0.0	6.84357E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99611E-07	0	0
I/M	None	None	0.984	N	0.769	0.33	0.532359089423	gnomAD-4.0.0	2.05312E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69891E-06	0	0
I/N	rs778290450	-2.639	0.995	N	0.795	0.479	0.767080534469	gnomAD-2.1.1	7.51E-05	None	None	None	None	N	None	0	1.69904E-04	None	5.81283E-04	0	None	0	None	0	5.48E-05	2.81452E-04
I/N	rs778290450	-2.639	0.995	N	0.795	0.479	0.767080534469	gnomAD-3.1.2	3.94E-05	None	None	None	None	N	None	2.41E-05	1.31148E-04	0	2.88018E-04	0	None	0	0	2.94E-05	0	0
I/N	rs778290450	-2.639	0.995	N	0.795	0.479	0.767080534469	gnomAD-4.0.0	2.29342E-05	None	None	None	None	N	None	1.33533E-05	1.5011E-04	None	3.04218E-04	0	None	0	0	1.18688E-05	0	6.40615E-05
I/T	rs778290450	-2.803	0.896	N	0.768	0.212	0.610115391599	gnomAD-2.1.1	2.86E-05	None	None	None	None	N	None	0	1.1327E-04	None	0	5.14E-05	None	0	None	0	2.35E-05	0
I/T	rs778290450	-2.803	0.896	N	0.768	0.212	0.610115391599	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93274E-04	None	0	0	0	0	0
I/T	rs778290450	-2.803	0.896	N	0.768	0.212	0.610115391599	gnomAD-4.0.0	8.05796E-06	None	None	None	None	N	None	0	6.67156E-05	None	0	2.23075E-05	None	0	0	6.78219E-06	0	0
I/V	rs397517713	None	0.004	N	0.232	0.069	0.385084120042	gnomAD-4.0.0	2.73743E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59844E-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	0.4132	ambiguous	0.3333	benign	-2.473	Highly Destabilizing	0.702	D	0.749	deleterious	None	None	None	None	N
I/C	0.7388	likely_pathogenic	0.7029	pathogenic	-1.873	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
I/D	0.8902	likely_pathogenic	0.856	pathogenic	-2.533	Highly Destabilizing	0.996	D	0.801	deleterious	None	None	None	None	N
I/E	0.8219	likely_pathogenic	0.7868	pathogenic	-2.383	Highly Destabilizing	0.988	D	0.789	deleterious	None	None	None	None	N
I/F	0.1992	likely_benign	0.1796	benign	-1.522	Destabilizing	0.984	D	0.769	deleterious	N	0.471595821	None	None	N
I/G	0.8436	likely_pathogenic	0.7921	pathogenic	-2.948	Highly Destabilizing	0.988	D	0.775	deleterious	None	None	None	None	N
I/H	0.6328	likely_pathogenic	0.5723	pathogenic	-2.231	Highly Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
I/K	0.7334	likely_pathogenic	0.6935	pathogenic	-1.928	Destabilizing	0.988	D	0.789	deleterious	None	None	None	None	N
I/L	0.1385	likely_benign	0.1325	benign	-1.141	Destabilizing	0.437	N	0.461	neutral	D	0.522692543	None	None	N
I/M	0.1088	likely_benign	0.0968	benign	-1.105	Destabilizing	0.984	D	0.769	deleterious	N	0.492929306	None	None	N
I/N	0.4197	ambiguous	0.3404	ambiguous	-2.078	Highly Destabilizing	0.995	D	0.795	deleterious	N	0.466035959	None	None	N
I/P	0.9896	likely_pathogenic	0.9818	pathogenic	-1.562	Destabilizing	0.996	D	0.805	deleterious	None	None	None	None	N
I/Q	0.6638	likely_pathogenic	0.6129	pathogenic	-2.076	Highly Destabilizing	0.996	D	0.805	deleterious	None	None	None	None	N
I/R	0.6285	likely_pathogenic	0.5726	pathogenic	-1.46	Destabilizing	0.996	D	0.803	deleterious	None	None	None	None	N
I/S	0.3612	ambiguous	0.2886	benign	-2.779	Highly Destabilizing	0.984	D	0.755	deleterious	N	0.47546648	None	None	N
I/T	0.1456	likely_benign	0.1099	benign	-2.497	Highly Destabilizing	0.896	D	0.768	deleterious	N	0.479517769	None	None	N
I/V	0.067	likely_benign	0.0692	benign	-1.562	Destabilizing	0.004	N	0.232	neutral	N	0.455968905	None	None	N
I/W	0.8026	likely_pathogenic	0.7804	pathogenic	-1.789	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
I/Y	0.5845	likely_pathogenic	0.5326	ambiguous	-1.545	Destabilizing	0.996	D	0.791	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.