TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23719	71380;71381;71382	chr2:178574977;178574976;178574975	chr2:179439704;179439703;179439702
N2AB	22078	66457;66458;66459	chr2:178574977;178574976;178574975	chr2:179439704;179439703;179439702
N2A	21151	63676;63677;63678	chr2:178574977;178574976;178574975	chr2:179439704;179439703;179439702
N2B	14654	44185;44186;44187	chr2:178574977;178574976;178574975	chr2:179439704;179439703;179439702
Novex-1	14779	44560;44561;44562	chr2:178574977;178574976;178574975	chr2:179439704;179439703;179439702
Novex-2	14846	44761;44762;44763	chr2:178574977;178574976;178574975	chr2:179439704;179439703;179439702
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-130
• Domain position: 83
• Structural Position: 172
• Q(SASA): 0.0769
• 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/V	rs201818722	-1.599	0.004	N	0.148	0.052	None	gnomAD-2.1.1	4.3E-05	None	None	None	None	N	None	4.96524E-04	0	None	0	0	None	0	None	0	0	0
I/V	rs201818722	-1.599	0.004	N	0.148	0.052	None	gnomAD-3.1.2	9.86E-05	None	None	None	None	N	None	3.61987E-04	0	0	0	0	None	0	0	0	0	0
I/V	rs201818722	-1.599	0.004	N	0.148	0.052	None	gnomAD-4.0.0	1.30179E-05	None	None	None	None	N	None	2.80381E-04	0	None	0	0	None	0	0	0	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	0.9458	likely_pathogenic	0.9219	pathogenic	-2.714	Highly Destabilizing	0.25	N	0.636	neutral	None	None	None	None	N
I/C	0.9412	likely_pathogenic	0.9206	pathogenic	-2.086	Highly Destabilizing	0.992	D	0.719	prob.delet.	None	None	None	None	N
I/D	0.999	likely_pathogenic	0.9982	pathogenic	-3.351	Highly Destabilizing	0.85	D	0.779	deleterious	None	None	None	None	N
I/E	0.9968	likely_pathogenic	0.995	pathogenic	-3.056	Highly Destabilizing	0.85	D	0.77	deleterious	None	None	None	None	N
I/F	0.4763	ambiguous	0.3853	ambiguous	-1.665	Destabilizing	0.81	D	0.728	prob.delet.	N	0.496349383	None	None	N
I/G	0.9935	likely_pathogenic	0.9894	pathogenic	-3.315	Highly Destabilizing	0.85	D	0.767	deleterious	None	None	None	None	N
I/H	0.9926	likely_pathogenic	0.9873	pathogenic	-2.867	Highly Destabilizing	0.992	D	0.752	deleterious	None	None	None	None	N
I/K	0.992	likely_pathogenic	0.9866	pathogenic	-2.414	Highly Destabilizing	0.85	D	0.771	deleterious	None	None	None	None	N
I/L	0.1705	likely_benign	0.1282	benign	-0.941	Destabilizing	0.002	N	0.153	neutral	N	0.508659745	None	None	N
I/M	0.2473	likely_benign	0.2103	benign	-0.919	Destabilizing	0.81	D	0.697	prob.neutral	N	0.488316584	None	None	N
I/N	0.9864	likely_pathogenic	0.9776	pathogenic	-3.008	Highly Destabilizing	0.81	D	0.785	deleterious	N	0.504952808	None	None	N
I/P	0.9947	likely_pathogenic	0.9904	pathogenic	-1.518	Destabilizing	0.92	D	0.785	deleterious	None	None	None	None	N
I/Q	0.9911	likely_pathogenic	0.9854	pathogenic	-2.729	Highly Destabilizing	0.92	D	0.782	deleterious	None	None	None	None	N
I/R	0.9876	likely_pathogenic	0.9785	pathogenic	-2.28	Highly Destabilizing	0.85	D	0.787	deleterious	None	None	None	None	N
I/S	0.9805	likely_pathogenic	0.969	pathogenic	-3.651	Highly Destabilizing	0.379	N	0.732	prob.delet.	N	0.484188754	None	None	N
I/T	0.9534	likely_pathogenic	0.9345	pathogenic	-3.187	Highly Destabilizing	0.004	N	0.451	neutral	N	0.518706167	None	None	N
I/V	0.1274	likely_benign	0.121	benign	-1.518	Destabilizing	0.004	N	0.148	neutral	N	0.480281065	None	None	N
I/W	0.9873	likely_pathogenic	0.9767	pathogenic	-2.09	Highly Destabilizing	0.992	D	0.765	deleterious	None	None	None	None	N
I/Y	0.9551	likely_pathogenic	0.9227	pathogenic	-1.8	Destabilizing	0.92	D	0.769	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.