TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7389	22390;22391;22392	chr2:178722734;178722733;178722732	chr2:179587461;179587460;179587459
N2AB	7072	21439;21440;21441	chr2:178722734;178722733;178722732	chr2:179587461;179587460;179587459
N2A	6145	18658;18659;18660	chr2:178722734;178722733;178722732	chr2:179587461;179587460;179587459
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-58
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.2069
• 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
D/E	None	None	0.433	D	0.347	0.53	0.508815697893	gnomAD-4.0.0	1.59282E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86053E-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
D/A	0.7149	likely_pathogenic	0.9019	pathogenic	2.094	Highly Stabilizing	1.0	D	0.785	deleterious	D	0.619030872	None	None	N
D/C	0.9456	likely_pathogenic	0.9847	pathogenic	1.573	Stabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
D/E	0.6398	likely_pathogenic	0.8199	pathogenic	0.113	Stabilizing	0.433	N	0.347	neutral	D	0.604354497	None	None	N
D/F	0.949	likely_pathogenic	0.9873	pathogenic	2.383	Highly Stabilizing	0.998	D	0.661	neutral	None	None	None	None	N
D/G	0.7638	likely_pathogenic	0.9295	pathogenic	1.626	Stabilizing	0.999	D	0.743	deleterious	D	0.640591824	None	None	N
D/H	0.7134	likely_pathogenic	0.8803	pathogenic	1.947	Stabilizing	1.0	D	0.747	deleterious	D	0.579502161	None	None	N
D/I	0.8925	likely_pathogenic	0.9709	pathogenic	3.333	Highly Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
D/K	0.9239	likely_pathogenic	0.9763	pathogenic	1.64	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
D/L	0.909	likely_pathogenic	0.9729	pathogenic	3.333	Highly Stabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
D/M	0.9586	likely_pathogenic	0.9894	pathogenic	3.375	Highly Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
D/N	0.3163	likely_benign	0.5516	ambiguous	0.796	Stabilizing	1.0	D	0.697	prob.neutral	D	0.597218113	None	None	N
D/P	0.9901	likely_pathogenic	0.9974	pathogenic	2.954	Highly Stabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
D/Q	0.8725	likely_pathogenic	0.9579	pathogenic	1.29	Stabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
D/R	0.9349	likely_pathogenic	0.9804	pathogenic	1.09	Stabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
D/S	0.4914	ambiguous	0.7678	pathogenic	0.538	Stabilizing	0.999	D	0.655	neutral	None	None	None	None	N
D/T	0.8016	likely_pathogenic	0.9378	pathogenic	1.008	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
D/V	0.7864	likely_pathogenic	0.9308	pathogenic	2.954	Highly Stabilizing	1.0	D	0.839	deleterious	D	0.657014794	None	None	N
D/W	0.9922	likely_pathogenic	0.9979	pathogenic	2.007	Highly Stabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
D/Y	0.7146	likely_pathogenic	0.9011	pathogenic	2.636	Highly Stabilizing	1.0	D	0.841	deleterious	D	0.640793629	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.