TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33536	100831;100832;100833	chr2:178536141;178536140;178536139	chr2:179400868;179400867;179400866
N2AB	31895	95908;95909;95910	chr2:178536141;178536140;178536139	chr2:179400868;179400867;179400866
N2A	30968	93127;93128;93129	chr2:178536141;178536140;178536139	chr2:179400868;179400867;179400866
N2B	24471	73636;73637;73638	chr2:178536141;178536140;178536139	chr2:179400868;179400867;179400866
Novex-1	24596	74011;74012;74013	chr2:178536141;178536140;178536139	chr2:179400868;179400867;179400866
Novex-2	24663	74212;74213;74214	chr2:178536141;178536140;178536139	chr2:179400868;179400867;179400866
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-158
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.0968
• 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	1.0	N	0.687	0.698	0.901312021487	gnomAD-4.0.0	1.36854E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79902E-06	0	0
I/T	None	None	0.995	N	0.626	0.639	0.778069038823	gnomAD-4.0.0	6.84268E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99509E-07	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	0.9669	likely_pathogenic	0.9467	pathogenic	-2.019	Highly Destabilizing	0.999	D	0.583	neutral	None	None	None	None	N
I/C	0.9683	likely_pathogenic	0.9504	pathogenic	-1.128	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
I/D	0.9979	likely_pathogenic	0.9966	pathogenic	-2.693	Highly Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
I/E	0.9933	likely_pathogenic	0.989	pathogenic	-2.417	Highly Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
I/F	0.7571	likely_pathogenic	0.6746	pathogenic	-1.308	Destabilizing	0.999	D	0.597	neutral	N	0.505259204	None	None	N
I/G	0.9939	likely_pathogenic	0.9897	pathogenic	-2.541	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
I/H	0.9933	likely_pathogenic	0.9889	pathogenic	-2.2	Highly Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
I/K	0.9871	likely_pathogenic	0.9813	pathogenic	-1.482	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
I/L	0.2197	likely_benign	0.1824	benign	-0.48	Destabilizing	0.026	N	0.222	neutral	N	0.483145225	None	None	N
I/M	0.3094	likely_benign	0.2763	benign	-0.465	Destabilizing	0.997	D	0.607	neutral	N	0.490686895	None	None	N
I/N	0.9764	likely_pathogenic	0.9644	pathogenic	-2.065	Highly Destabilizing	1.0	D	0.795	deleterious	N	0.517794052	None	None	N
I/P	0.996	likely_pathogenic	0.9939	pathogenic	-0.98	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
I/Q	0.9878	likely_pathogenic	0.9802	pathogenic	-1.797	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
I/R	0.9831	likely_pathogenic	0.9756	pathogenic	-1.557	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
I/S	0.9867	likely_pathogenic	0.9799	pathogenic	-2.596	Highly Destabilizing	1.0	D	0.687	prob.neutral	N	0.511691212	None	None	N
I/T	0.9688	likely_pathogenic	0.9525	pathogenic	-2.167	Highly Destabilizing	0.995	D	0.626	neutral	N	0.511536174	None	None	N
I/V	0.1671	likely_benign	0.15	benign	-0.98	Destabilizing	0.262	N	0.216	neutral	N	0.483958875	None	None	N
I/W	0.99	likely_pathogenic	0.9852	pathogenic	-1.701	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
I/Y	0.9708	likely_pathogenic	0.9525	pathogenic	-1.34	Destabilizing	0.999	D	0.716	prob.delet.	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.