TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15742	47449;47450;47451	chr2:178618234;178618233;178618232	chr2:179482961;179482960;179482959
N2AB	14101	42526;42527;42528	chr2:178618234;178618233;178618232	chr2:179482961;179482960;179482959
N2A	13174	39745;39746;39747	chr2:178618234;178618233;178618232	chr2:179482961;179482960;179482959
N2B	6677	20254;20255;20256	chr2:178618234;178618233;178618232	chr2:179482961;179482960;179482959
Novex-1	6802	20629;20630;20631	chr2:178618234;178618233;178618232	chr2:179482961;179482960;179482959
Novex-2	6869	20830;20831;20832	chr2:178618234;178618233;178618232	chr2:179482961;179482960;179482959
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-1
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.607
• Predicted PPI site: I

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	rs1209372495	-0.488	0.98	D	0.636	0.311	0.420199648628	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/G	rs1209372495	-0.488	0.98	D	0.636	0.311	0.420199648628	gnomAD-4.0.0	1.59321E-06	None	None	None	None	I	None	0	2.2876E-05	None	0	0	None	0	0	0	0	0
E/K	rs1233336228	0.684	0.98	N	0.601	0.255	0.339316883193	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
E/K	rs1233336228	0.684	0.98	N	0.601	0.255	0.339316883193	gnomAD-4.0.0	4.77969E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.58674E-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	0.1472	likely_benign	0.1343	benign	-0.285	Destabilizing	0.961	D	0.62	neutral	N	0.481468864	None	None	I
E/C	0.8324	likely_pathogenic	0.7352	pathogenic	0.017	Stabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
E/D	0.1085	likely_benign	0.0996	benign	-0.309	Destabilizing	0.954	D	0.559	neutral	N	0.480728709	None	None	I
E/F	0.6972	likely_pathogenic	0.5946	pathogenic	-0.207	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	I
E/G	0.2005	likely_benign	0.1906	benign	-0.455	Destabilizing	0.98	D	0.636	neutral	D	0.563366916	None	None	I
E/H	0.4829	ambiguous	0.3968	ambiguous	0.092	Stabilizing	0.999	D	0.565	neutral	None	None	None	None	I
E/I	0.2827	likely_benign	0.2144	benign	0.118	Stabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	I
E/K	0.1288	likely_benign	0.1165	benign	0.508	Stabilizing	0.98	D	0.601	neutral	N	0.481954699	None	None	I
E/L	0.2925	likely_benign	0.2354	benign	0.118	Stabilizing	0.996	D	0.629	neutral	None	None	None	None	I
E/M	0.3922	ambiguous	0.3265	benign	0.164	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
E/N	0.2307	likely_benign	0.1933	benign	0.154	Stabilizing	0.999	D	0.573	neutral	None	None	None	None	I
E/P	0.3038	likely_benign	0.2598	benign	0.003	Stabilizing	0.041	N	0.298	neutral	None	None	None	None	I
E/Q	0.1304	likely_benign	0.1198	benign	0.181	Stabilizing	0.993	D	0.603	neutral	N	0.480660524	None	None	I
E/R	0.2467	likely_benign	0.2112	benign	0.66	Stabilizing	0.999	D	0.578	neutral	None	None	None	None	I
E/S	0.19	likely_benign	0.1653	benign	0.031	Stabilizing	0.985	D	0.573	neutral	None	None	None	None	I
E/T	0.2087	likely_benign	0.1776	benign	0.177	Stabilizing	0.985	D	0.651	neutral	None	None	None	None	I
E/V	0.1792	likely_benign	0.1451	benign	0.003	Stabilizing	0.994	D	0.598	neutral	N	0.481524991	None	None	I
E/W	0.8952	likely_pathogenic	0.8481	pathogenic	-0.071	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
E/Y	0.5904	likely_pathogenic	0.4804	ambiguous	0.042	Stabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	I

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.