TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5706	17341;17342;17343	chr2:178731759;178731758;178731757	chr2:179596486;179596485;179596484
N2AB	5389	16390;16391;16392	chr2:178731759;178731758;178731757	chr2:179596486;179596485;179596484
N2A	4462	13609;13610;13611	chr2:178731759;178731758;178731757	chr2:179596486;179596485;179596484
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-40
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.3651
• 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
E/A	None	None	0.012	N	0.392	0.18	0.298403945805	gnomAD-4.0.0	6.84234E-07	None	None	None	None	I	None	2.98811E-05	0	None	0	0	None	0	0	0	0	0
E/G	rs1176874608	-1.534	0.055	N	0.536	0.255	0.353336612579	gnomAD-4.0.0	6.84234E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15947E-05	0
E/K	rs376593556	-0.018	None	N	0.189	0.128	None	gnomAD-2.1.1	4.65E-05	None	None	None	None	I	None	4.96278E-04	2.83E-05	None	0	0	None	0	None	0	0	0
E/K	rs376593556	-0.018	None	N	0.189	0.128	None	gnomAD-3.1.2	1.77459E-04	None	None	None	None	I	None	5.79151E-04	0	0	0	0	None	0	0	4.41E-05	0	0
E/K	rs376593556	-0.018	None	N	0.189	0.128	None	gnomAD-4.0.0	4.02818E-05	None	None	None	None	I	None	6.00737E-04	1.66711E-05	None	0	0	None	0	0	1.01715E-05	3.29431E-05	6.40512E-05
E/Q	rs376593556	None	0.006	N	0.271	0.128	0.149567049428	gnomAD-4.0.0	6.84237E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15958E-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
E/A	0.1695	likely_benign	0.157	benign	-0.687	Destabilizing	0.012	N	0.392	neutral	N	0.488441488	None	None	I
E/C	0.8213	likely_pathogenic	0.7918	pathogenic	-0.234	Destabilizing	0.864	D	0.585	neutral	None	None	None	None	I
E/D	0.1038	likely_benign	0.1048	benign	-1.07	Destabilizing	0.024	N	0.433	neutral	N	0.481534646	None	None	I
E/F	0.6076	likely_pathogenic	0.5664	pathogenic	-0.638	Destabilizing	0.356	N	0.598	neutral	None	None	None	None	I
E/G	0.2346	likely_benign	0.2168	benign	-0.993	Destabilizing	0.055	N	0.536	neutral	N	0.504939582	None	None	I
E/H	0.4099	ambiguous	0.3648	ambiguous	-0.98	Destabilizing	0.356	N	0.54	neutral	None	None	None	None	I
E/I	0.2381	likely_benign	0.2147	benign	0.126	Stabilizing	0.038	N	0.567	neutral	None	None	None	None	I
E/K	0.1519	likely_benign	0.1378	benign	-0.313	Destabilizing	None	N	0.189	neutral	N	0.479723705	None	None	I
E/L	0.3075	likely_benign	0.28	benign	0.126	Stabilizing	0.016	N	0.501	neutral	None	None	None	None	I
E/M	0.3636	ambiguous	0.325	benign	0.596	Stabilizing	0.356	N	0.588	neutral	None	None	None	None	I
E/N	0.182	likely_benign	0.1692	benign	-0.629	Destabilizing	0.072	N	0.403	neutral	None	None	None	None	I
E/P	0.682	likely_pathogenic	0.6904	pathogenic	-0.123	Destabilizing	0.136	N	0.569	neutral	None	None	None	None	I
E/Q	0.1474	likely_benign	0.134	benign	-0.565	Destabilizing	0.006	N	0.271	neutral	N	0.486671107	None	None	I
E/R	0.2721	likely_benign	0.2461	benign	-0.257	Destabilizing	0.038	N	0.411	neutral	None	None	None	None	I
E/S	0.1945	likely_benign	0.1813	benign	-0.911	Destabilizing	0.003	N	0.203	neutral	None	None	None	None	I
E/T	0.1877	likely_benign	0.1735	benign	-0.657	Destabilizing	0.001	N	0.27	neutral	None	None	None	None	I
E/V	0.1664	likely_benign	0.1528	benign	-0.123	Destabilizing	0.001	N	0.419	neutral	N	0.468605421	None	None	I
E/W	0.8271	likely_pathogenic	0.7927	pathogenic	-0.536	Destabilizing	0.864	D	0.592	neutral	None	None	None	None	I
E/Y	0.4888	ambiguous	0.4499	ambiguous	-0.4	Destabilizing	0.356	N	0.597	neutral	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.