TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21991	66196;66197;66198	chr2:178582485;178582484;178582483	chr2:179447212;179447211;179447210
N2AB	20350	61273;61274;61275	chr2:178582485;178582484;178582483	chr2:179447212;179447211;179447210
N2A	19423	58492;58493;58494	chr2:178582485;178582484;178582483	chr2:179447212;179447211;179447210
N2B	12926	39001;39002;39003	chr2:178582485;178582484;178582483	chr2:179447212;179447211;179447210
Novex-1	13051	39376;39377;39378	chr2:178582485;178582484;178582483	chr2:179447212;179447211;179447210
Novex-2	13118	39577;39578;39579	chr2:178582485;178582484;178582483	chr2:179447212;179447211;179447210
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-47
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.1064
• 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
Y/D	None	None	1.0	D	0.896	0.9	0.894210320649	gnomAD-4.0.0	1.5932E-06	None	None	None	None	N	None	0	2.28822E-05	None	0	0	None	0	0	0	0	0
Y/H	rs1407550215	None	1.0	D	0.823	0.878	0.775338622076	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
Y/H	rs1407550215	None	1.0	D	0.823	0.878	0.775338622076	gnomAD-4.0.0	1.31506E-05	None	None	None	None	N	None	2.41348E-05	0	None	0	0	None	0	0	1.47089E-05	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
Y/A	0.9994	likely_pathogenic	0.999	pathogenic	-3.71	Highly Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
Y/C	0.9813	likely_pathogenic	0.9696	pathogenic	-2.119	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.662799268	None	None	N
Y/D	0.9992	likely_pathogenic	0.9988	pathogenic	-3.89	Highly Destabilizing	1.0	D	0.896	deleterious	D	0.663001072	None	None	N
Y/E	0.9998	likely_pathogenic	0.9997	pathogenic	-3.686	Highly Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
Y/F	0.3	likely_benign	0.2679	benign	-1.423	Destabilizing	0.999	D	0.679	prob.neutral	D	0.56975304	None	None	N
Y/G	0.9976	likely_pathogenic	0.9964	pathogenic	-4.089	Highly Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
Y/H	0.9937	likely_pathogenic	0.9897	pathogenic	-2.668	Highly Destabilizing	1.0	D	0.823	deleterious	D	0.66239566	None	None	N
Y/I	0.9922	likely_pathogenic	0.9876	pathogenic	-2.412	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
Y/K	0.9997	likely_pathogenic	0.9995	pathogenic	-2.555	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
Y/L	0.9833	likely_pathogenic	0.9783	pathogenic	-2.412	Highly Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
Y/M	0.9961	likely_pathogenic	0.9941	pathogenic	-2.165	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
Y/N	0.9955	likely_pathogenic	0.9928	pathogenic	-3.27	Highly Destabilizing	1.0	D	0.882	deleterious	D	0.662799268	None	None	N
Y/P	0.9999	likely_pathogenic	0.9998	pathogenic	-2.865	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
Y/Q	0.9997	likely_pathogenic	0.9994	pathogenic	-3.044	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/R	0.9984	likely_pathogenic	0.9974	pathogenic	-2.239	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
Y/S	0.9977	likely_pathogenic	0.9963	pathogenic	-3.589	Highly Destabilizing	1.0	D	0.897	deleterious	D	0.662799268	None	None	N
Y/T	0.9991	likely_pathogenic	0.9985	pathogenic	-3.277	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
Y/V	0.9859	likely_pathogenic	0.9801	pathogenic	-2.865	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
Y/W	0.9189	likely_pathogenic	0.9023	pathogenic	-0.612	Destabilizing	1.0	D	0.808	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.