TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29570	88933;88934;88935	chr2:178554639;178554638;178554637	chr2:179419366;179419365;179419364
N2AB	27929	84010;84011;84012	chr2:178554639;178554638;178554637	chr2:179419366;179419365;179419364
N2A	27002	81229;81230;81231	chr2:178554639;178554638;178554637	chr2:179419366;179419365;179419364
N2B	20505	61738;61739;61740	chr2:178554639;178554638;178554637	chr2:179419366;179419365;179419364
Novex-1	20630	62113;62114;62115	chr2:178554639;178554638;178554637	chr2:179419366;179419365;179419364
Novex-2	20697	62314;62315;62316	chr2:178554639;178554638;178554637	chr2:179419366;179419365;179419364
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: Fn3-103
• Domain position: 38
• Structural Position: 39
• Q(SASA): 0.0988
• 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	rs139506970	None	0.58	N	0.418	0.061	0.549964211903	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	1.30993E-04	0	0	0	None	0	0	0	0	0
I/L	rs139506970	None	0.58	N	0.418	0.061	0.549964211903	gnomAD-4.0.0	1.85903E-06	None	None	None	None	N	None	0	5.00067E-05	None	0	0	None	0	0	0	0	0
I/T	rs965795447	-3.327	0.939	N	0.675	0.391	0.680584855444	gnomAD-2.1.1	6.37E-05	None	None	None	None	N	None	2.29463E-04	0	None	0	0	None	0	None	0	0	0
I/T	rs965795447	-3.327	0.939	N	0.675	0.391	0.680584855444	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
I/T	rs965795447	-3.327	0.939	N	0.675	0.391	0.680584855444	gnomAD-4.0.0	4.06004E-06	None	None	None	None	N	None	6.99252E-05	0	None	0	0	None	0	0	0	0	0
I/V	rs139506970	-2.338	0.02	N	0.233	0.041	None	gnomAD-2.1.1	8.24753E-04	None	None	None	None	N	None	8.63565E-03	1.41411E-04	None	0	0	None	3.27E-05	None	0	1.01613E-04	4.20994E-04
I/V	rs139506970	-2.338	0.02	N	0.233	0.041	None	gnomAD-3.1.2	2.43258E-03	None	None	None	None	N	None	8.28062E-03	8.51454E-04	0	0	0	None	0	0	1.32326E-04	2.07297E-04	1.91205E-03
I/V	rs139506970	-2.338	0.02	N	0.233	0.041	None	1000 genomes	3.39457E-03	None	None	None	None	N	None	1.21E-02	1.4E-03	None	None	0	0	None	None	None	0	None
I/V	rs139506970	-2.338	0.02	N	0.233	0.041	None	gnomAD-4.0.0	5.00663E-04	None	None	None	None	N	None	8.45085E-03	3.9992E-04	None	0	0	None	0	2.30947E-03	6.78065E-05	3.29388E-05	8.48217E-04

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	0.3757	ambiguous	0.4313	ambiguous	-2.759	Highly Destabilizing	0.91	D	0.649	neutral	None	None	None	None	N
I/C	0.7295	likely_pathogenic	0.7701	pathogenic	-1.992	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
I/D	0.9188	likely_pathogenic	0.936	pathogenic	-3.454	Highly Destabilizing	0.998	D	0.734	prob.delet.	None	None	None	None	N
I/E	0.7936	likely_pathogenic	0.8096	pathogenic	-3.276	Highly Destabilizing	0.993	D	0.719	prob.delet.	None	None	None	None	N
I/F	0.2979	likely_benign	0.3466	ambiguous	-1.671	Destabilizing	0.991	D	0.703	prob.neutral	N	0.499317038	None	None	N
I/G	0.8539	likely_pathogenic	0.8926	pathogenic	-3.221	Highly Destabilizing	0.993	D	0.725	prob.delet.	None	None	None	None	N
I/H	0.6904	likely_pathogenic	0.7439	pathogenic	-2.714	Highly Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
I/K	0.6228	likely_pathogenic	0.6584	pathogenic	-2.272	Highly Destabilizing	0.993	D	0.715	prob.delet.	None	None	None	None	N
I/L	0.1653	likely_benign	0.1716	benign	-1.419	Destabilizing	0.58	D	0.418	neutral	N	0.492524352	None	None	N
I/M	0.1385	likely_benign	0.1481	benign	-1.282	Destabilizing	0.991	D	0.677	prob.neutral	N	0.466760429	None	None	N
I/N	0.5925	likely_pathogenic	0.6412	pathogenic	-2.545	Highly Destabilizing	0.997	D	0.741	deleterious	N	0.49810353	None	None	N
I/P	0.9866	likely_pathogenic	0.9903	pathogenic	-1.851	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
I/Q	0.6585	likely_pathogenic	0.6893	pathogenic	-2.471	Highly Destabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	N
I/R	0.4896	ambiguous	0.542	ambiguous	-1.81	Destabilizing	0.993	D	0.739	prob.delet.	None	None	None	None	N
I/S	0.4449	ambiguous	0.495	ambiguous	-3.091	Highly Destabilizing	0.991	D	0.677	prob.neutral	N	0.501007762	None	None	N
I/T	0.1546	likely_benign	0.1811	benign	-2.805	Highly Destabilizing	0.939	D	0.675	prob.neutral	N	0.422144333	None	None	N
I/V	0.0638	likely_benign	0.0671	benign	-1.851	Destabilizing	0.02	N	0.233	neutral	N	0.427686226	None	None	N
I/W	0.8847	likely_pathogenic	0.9184	pathogenic	-2.16	Highly Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
I/Y	0.6971	likely_pathogenic	0.7493	pathogenic	-1.956	Destabilizing	0.998	D	0.655	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.