TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7626	23101;23102;23103	chr2:178721143;178721142;178721141	chr2:179585870;179585869;179585868
N2AB	7309	22150;22151;22152	chr2:178721143;178721142;178721141	chr2:179585870;179585869;179585868
N2A	6382	19369;19370;19371	chr2:178721143;178721142;178721141	chr2:179585870;179585869;179585868
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-61
• Domain position: 19
• Structural Position: 28
• Q(SASA): 0.2095
• 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	rs1560677297	None	None	N	0.185	0.098	0.207176502487	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	9.19118E-04
I/L	rs1560677297	None	None	N	0.185	0.098	0.207176502487	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
I/L	rs1560677297	None	None	N	0.185	0.098	0.207176502487	gnomAD-4.0.0	6.57065E-06	None	None	None	None	N	None	0	6.54965E-05	None	0	0	None	0	0	0	0	0
I/V	None	None	None	N	0.158	0.07	0.19670166235	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

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	0.4437	ambiguous	0.3493	ambiguous	-2.074	Highly Destabilizing	0.002	N	0.452	neutral	None	None	None	None	N
I/C	0.7018	likely_pathogenic	0.6473	pathogenic	-1.73	Destabilizing	None	N	0.448	neutral	None	None	None	None	N
I/D	0.9167	likely_pathogenic	0.8748	pathogenic	-1.222	Destabilizing	0.044	N	0.642	neutral	None	None	None	None	N
I/E	0.84	likely_pathogenic	0.7928	pathogenic	-1.154	Destabilizing	0.044	N	0.637	neutral	None	None	None	None	N
I/F	0.1584	likely_benign	0.1542	benign	-1.371	Destabilizing	0.033	N	0.604	neutral	N	0.456979265	None	None	N
I/G	0.8045	likely_pathogenic	0.7204	pathogenic	-2.476	Highly Destabilizing	0.009	N	0.576	neutral	None	None	None	None	N
I/H	0.7044	likely_pathogenic	0.6424	pathogenic	-1.519	Destabilizing	0.497	N	0.695	prob.neutral	None	None	None	None	N
I/K	0.7549	likely_pathogenic	0.6865	pathogenic	-1.49	Destabilizing	0.018	N	0.628	neutral	None	None	None	None	N
I/L	0.1159	likely_benign	0.1043	benign	-1.007	Destabilizing	None	N	0.185	neutral	N	0.386249743	None	None	N
I/M	0.1378	likely_benign	0.1229	benign	-0.993	Destabilizing	0.108	N	0.597	neutral	N	0.502212909	None	None	N
I/N	0.5994	likely_pathogenic	0.5062	ambiguous	-1.444	Destabilizing	0.033	N	0.685	prob.neutral	N	0.467924247	None	None	N
I/P	0.9263	likely_pathogenic	0.8866	pathogenic	-1.333	Destabilizing	None	N	0.519	neutral	None	None	None	None	N
I/Q	0.7107	likely_pathogenic	0.6413	pathogenic	-1.528	Destabilizing	0.085	N	0.728	prob.delet.	None	None	None	None	N
I/R	0.6542	likely_pathogenic	0.5649	pathogenic	-0.933	Destabilizing	0.044	N	0.713	prob.delet.	None	None	None	None	N
I/S	0.4723	ambiguous	0.3636	ambiguous	-2.229	Highly Destabilizing	None	N	0.422	neutral	N	0.502386268	None	None	N
I/T	0.3422	ambiguous	0.2653	benign	-2.016	Highly Destabilizing	None	N	0.38	neutral	N	0.433083685	None	None	N
I/V	0.0717	likely_benign	0.0684	benign	-1.333	Destabilizing	None	N	0.158	neutral	N	0.374029808	None	None	N
I/W	0.8238	likely_pathogenic	0.7914	pathogenic	-1.387	Destabilizing	0.788	D	0.683	prob.neutral	None	None	None	None	N
I/Y	0.5979	likely_pathogenic	0.5493	ambiguous	-1.197	Destabilizing	0.245	N	0.699	prob.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.