TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2640	8143;8144;8145	chr2:178771409;178771408;178771407	chr2:179636136;179636135;179636134
N2AB	2640	8143;8144;8145	chr2:178771409;178771408;178771407	chr2:179636136;179636135;179636134
N2A	2640	8143;8144;8145	chr2:178771409;178771408;178771407	chr2:179636136;179636135;179636134
N2B	2594	8005;8006;8007	chr2:178771409;178771408;178771407	chr2:179636136;179636135;179636134
Novex-1	2594	8005;8006;8007	chr2:178771409;178771408;178771407	chr2:179636136;179636135;179636134
Novex-2	2594	8005;8006;8007	chr2:178771409;178771408;178771407	chr2:179636136;179636135;179636134
Novex-3	2640	8143;8144;8145	chr2:178771409;178771408;178771407	chr2:179636136;179636135;179636134

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-16
• Domain position: 20
• Structural Position: 31
• Q(SASA): 0.5196
• 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
E/G	rs1343185312	-1.134	1.0	D	0.731	0.646	0.609393688558	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.81E-06	0
E/G	rs1343185312	-1.134	1.0	D	0.731	0.646	0.609393688558	gnomAD-4.0.0	2.05242E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69814E-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
E/A	0.2114	likely_benign	0.215	benign	-0.933	Destabilizing	0.999	D	0.674	neutral	D	0.660259061	None	None	N
E/C	0.8699	likely_pathogenic	0.862	pathogenic	-0.659	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
E/D	0.3525	ambiguous	0.375	ambiguous	-1.361	Destabilizing	0.999	D	0.471	neutral	D	0.566730592	None	None	N
E/F	0.7796	likely_pathogenic	0.7753	pathogenic	-0.549	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/G	0.3593	ambiguous	0.3554	ambiguous	-1.295	Destabilizing	1.0	D	0.731	prob.delet.	D	0.624274278	None	None	N
E/H	0.597	likely_pathogenic	0.5741	pathogenic	-0.916	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	N
E/I	0.3004	likely_benign	0.3018	benign	0.057	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/K	0.3317	likely_benign	0.298	benign	-1.042	Destabilizing	0.999	D	0.569	neutral	N	0.501827228	None	None	N
E/L	0.4757	ambiguous	0.459	ambiguous	0.057	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/M	0.5117	ambiguous	0.5025	ambiguous	0.522	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/N	0.5144	ambiguous	0.5301	ambiguous	-1.362	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/P	0.9806	likely_pathogenic	0.9728	pathogenic	-0.253	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/Q	0.1822	likely_benign	0.1744	benign	-1.233	Destabilizing	1.0	D	0.601	neutral	N	0.512123715	None	None	N
E/R	0.4728	ambiguous	0.4321	ambiguous	-0.797	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/S	0.247	likely_benign	0.2623	benign	-1.72	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
E/T	0.2204	likely_benign	0.2297	benign	-1.429	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/V	0.1965	likely_benign	0.1957	benign	-0.253	Destabilizing	1.0	D	0.749	deleterious	D	0.57436629	None	None	N
E/W	0.9293	likely_pathogenic	0.92	pathogenic	-0.411	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/Y	0.7279	likely_pathogenic	0.7121	pathogenic	-0.344	Destabilizing	1.0	D	0.761	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.