TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7428	22507;22508;22509	chr2:178722505;178722504;178722503	chr2:179587232;179587231;179587230
N2AB	7111	21556;21557;21558	chr2:178722505;178722504;178722503	chr2:179587232;179587231;179587230
N2A	6184	18775;18776;18777	chr2:178722505;178722504;178722503	chr2:179587232;179587231;179587230
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: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-59
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.1949
• 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/S	None	None	0.062	N	0.399	0.328	0.807768874225	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
I/V	rs1211184600	-1.078	None	N	0.115	0.035	0.358744678677	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
I/V	rs1211184600	-1.078	None	N	0.115	0.035	0.358744678677	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs1211184600	-1.078	None	N	0.115	0.035	0.358744678677	gnomAD-4.0.0	1.85966E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54345E-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	0.1493	likely_benign	0.1466	benign	-1.545	Destabilizing	0.035	N	0.372	neutral	None	None	None	None	N
I/C	0.7021	likely_pathogenic	0.705	pathogenic	-0.97	Destabilizing	0.824	D	0.339	neutral	None	None	None	None	N
I/D	0.6139	likely_pathogenic	0.5658	pathogenic	-1.07	Destabilizing	0.38	N	0.449	neutral	None	None	None	None	N
I/E	0.4185	ambiguous	0.3789	ambiguous	-1.074	Destabilizing	0.38	N	0.457	neutral	None	None	None	None	N
I/F	0.15	likely_benign	0.1442	benign	-1.091	Destabilizing	0.317	N	0.374	neutral	N	0.493583276	None	None	N
I/G	0.5067	ambiguous	0.4784	ambiguous	-1.867	Destabilizing	0.149	N	0.464	neutral	None	None	None	None	N
I/H	0.4521	ambiguous	0.4414	ambiguous	-1.184	Destabilizing	0.935	D	0.431	neutral	None	None	None	None	N
I/K	0.2895	likely_benign	0.2733	benign	-1.13	Destabilizing	0.38	N	0.465	neutral	None	None	None	None	N
I/L	0.1138	likely_benign	0.1192	benign	-0.743	Destabilizing	None	N	0.074	neutral	N	0.45690556	None	None	N
I/M	0.0742	likely_benign	0.0791	benign	-0.598	Destabilizing	0.317	N	0.388	neutral	N	0.477302262	None	None	N
I/N	0.284	likely_benign	0.2631	benign	-0.91	Destabilizing	0.317	N	0.454	neutral	D	0.537966719	None	None	N
I/P	0.8297	likely_pathogenic	0.8045	pathogenic	-0.978	Destabilizing	0.555	D	0.453	neutral	None	None	None	None	N
I/Q	0.3245	likely_benign	0.3073	benign	-1.082	Destabilizing	0.555	D	0.455	neutral	None	None	None	None	N
I/R	0.212	likely_benign	0.204	benign	-0.567	Destabilizing	0.38	N	0.451	neutral	None	None	None	None	N
I/S	0.189	likely_benign	0.1916	benign	-1.484	Destabilizing	0.062	N	0.399	neutral	N	0.496061381	None	None	N
I/T	0.0749	likely_benign	0.0772	benign	-1.371	Destabilizing	0.002	N	0.223	neutral	N	0.442920329	None	None	N
I/V	0.0665	likely_benign	0.0633	benign	-0.978	Destabilizing	None	N	0.115	neutral	N	0.40449244	None	None	N
I/W	0.6919	likely_pathogenic	0.6794	pathogenic	-1.177	Destabilizing	0.935	D	0.474	neutral	None	None	None	None	N
I/Y	0.5372	ambiguous	0.5058	ambiguous	-0.954	Destabilizing	0.555	D	0.364	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.