TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31815	95668;95669;95670	chr2:178545667;178545666;178545665	chr2:179410394;179410393;179410392
N2AB	30174	90745;90746;90747	chr2:178545667;178545666;178545665	chr2:179410394;179410393;179410392
N2A	29247	87964;87965;87966	chr2:178545667;178545666;178545665	chr2:179410394;179410393;179410392
N2B	22750	68473;68474;68475	chr2:178545667;178545666;178545665	chr2:179410394;179410393;179410392
Novex-1	22875	68848;68849;68850	chr2:178545667;178545666;178545665	chr2:179410394;179410393;179410392
Novex-2	22942	69049;69050;69051	chr2:178545667;178545666;178545665	chr2:179410394;179410393;179410392
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-120
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3092
• 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/K	rs779953291	-0.442	0.37	N	0.48	0.225	0.297375071883	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
E/K	rs779953291	-0.442	0.37	N	0.48	0.225	0.297375071883	gnomAD-4.0.0	2.05303E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7993E-06	1.15969E-05	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	0.1595	likely_benign	0.1639	benign	-0.541	Destabilizing	0.978	D	0.559	neutral	N	0.480825759	None	None	N
E/C	0.7211	likely_pathogenic	0.7622	pathogenic	-0.278	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
E/D	0.1803	likely_benign	0.2053	benign	-0.627	Destabilizing	0.121	N	0.434	neutral	N	0.491118881	None	None	N
E/F	0.6845	likely_pathogenic	0.7179	pathogenic	-0.21	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/G	0.2199	likely_benign	0.2213	benign	-0.801	Destabilizing	0.978	D	0.634	neutral	N	0.480269555	None	None	N
E/H	0.385	ambiguous	0.4031	ambiguous	-0.148	Destabilizing	1.0	D	0.547	neutral	None	None	None	None	N
E/I	0.2457	likely_benign	0.2835	benign	0.134	Stabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
E/K	0.1191	likely_benign	0.1144	benign	-0.055	Destabilizing	0.37	N	0.48	neutral	N	0.507645733	None	None	N
E/L	0.3044	likely_benign	0.3188	benign	0.134	Stabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
E/M	0.3329	likely_benign	0.3541	ambiguous	0.248	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/N	0.2556	likely_benign	0.2943	benign	-0.454	Destabilizing	0.995	D	0.513	neutral	None	None	None	None	N
E/P	0.9406	likely_pathogenic	0.9331	pathogenic	-0.07	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
E/Q	0.1109	likely_benign	0.1098	benign	-0.386	Destabilizing	0.994	D	0.499	neutral	N	0.502490629	None	None	N
E/R	0.2029	likely_benign	0.1976	benign	0.229	Stabilizing	0.99	D	0.501	neutral	None	None	None	None	N
E/S	0.1901	likely_benign	0.2056	benign	-0.638	Destabilizing	0.983	D	0.433	neutral	None	None	None	None	N
E/T	0.1598	likely_benign	0.1778	benign	-0.428	Destabilizing	0.998	D	0.654	neutral	None	None	None	None	N
E/V	0.1455	likely_benign	0.1589	benign	-0.07	Destabilizing	0.997	D	0.705	prob.neutral	N	0.508379238	None	None	N
E/W	0.8629	likely_pathogenic	0.8734	pathogenic	-0.003	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
E/Y	0.587	likely_pathogenic	0.6129	pathogenic	0.033	Stabilizing	0.999	D	0.749	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.