TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33179	99760;99761;99762	chr2:178537672;178537671;178537670	chr2:179402399;179402398;179402397
N2AB	31538	94837;94838;94839	chr2:178537672;178537671;178537670	chr2:179402399;179402398;179402397
N2A	30611	92056;92057;92058	chr2:178537672;178537671;178537670	chr2:179402399;179402398;179402397
N2B	24114	72565;72566;72567	chr2:178537672;178537671;178537670	chr2:179402399;179402398;179402397
Novex-1	24239	72940;72941;72942	chr2:178537672;178537671;178537670	chr2:179402399;179402398;179402397
Novex-2	24306	73141;73142;73143	chr2:178537672;178537671;178537670	chr2:179402399;179402398;179402397
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-156
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.3273
• 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
V/A	rs576759867	-0.626	0.001	N	0.261	0.228	0.379366414296	gnomAD-2.1.1	6.06E-05	None	None	None	None	I	None	8.27E-05	1.98166E-04	None	0	0	None	2.28773E-04	None	0	7.8E-06	0
V/A	rs576759867	-0.626	0.001	N	0.261	0.228	0.379366414296	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	2.41E-05	6.56E-05	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs576759867	-0.626	0.001	N	0.261	0.228	0.379366414296	gnomAD-4.0.0	2.97466E-05	None	None	None	None	I	None	8.01303E-05	1.50105E-04	None	0	2.22806E-05	None	0	3.28947E-04	6.78087E-06	1.86637E-04	8.00589E-05
V/D	None	-0.31	0.976	N	0.599	0.522	0.775623232837	gnomAD-2.1.1	2.81E-05	None	None	None	None	I	None	0	2.0304E-04	None	0	0	None	0	None	0	0	0
V/D	None	-0.31	0.976	N	0.599	0.522	0.775623232837	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/D	None	-0.31	0.976	N	0.599	0.522	0.775623232837	gnomAD-4.0.0	4.95777E-06	None	None	None	None	I	None	1.33551E-05	1.16748E-04	None	0	0	None	0	0	0	0	0
V/F	rs1452847129	None	0.989	N	0.491	0.401	0.667001395416	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/F	rs1452847129	None	0.989	N	0.491	0.401	0.667001395416	gnomAD-4.0.0	6.57177E-06	None	None	None	None	I	None	2.4122E-05	0	None	0	0	None	0	0	0	0	0
V/G	rs576759867	None	0.793	N	0.53	0.393	0.69196344514	gnomAD-4.0.0	6.84213E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99459E-07	0	0
V/I	rs1452847129	-0.307	0.128	N	0.412	0.143	0.448000600372	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.86E-06	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
V/A	0.0975	likely_benign	0.1234	benign	-0.31	Destabilizing	0.001	N	0.261	neutral	N	0.437415722	None	None	I
V/C	0.6914	likely_pathogenic	0.7534	pathogenic	-0.7	Destabilizing	0.996	D	0.517	neutral	None	None	None	None	I
V/D	0.4815	ambiguous	0.5495	ambiguous	-0.379	Destabilizing	0.976	D	0.599	neutral	N	0.497572975	None	None	I
V/E	0.4269	ambiguous	0.4669	ambiguous	-0.504	Destabilizing	0.809	D	0.531	neutral	None	None	None	None	I
V/F	0.1407	likely_benign	0.171	benign	-0.687	Destabilizing	0.989	D	0.491	neutral	N	0.489076694	None	None	I
V/G	0.2406	likely_benign	0.2895	benign	-0.382	Destabilizing	0.793	D	0.53	neutral	N	0.515993936	None	None	I
V/H	0.5836	likely_pathogenic	0.6346	pathogenic	0.02	Stabilizing	0.997	D	0.627	neutral	None	None	None	None	I
V/I	0.0937	likely_benign	0.1037	benign	-0.272	Destabilizing	0.128	N	0.412	neutral	N	0.458004425	None	None	I
V/K	0.5469	ambiguous	0.5981	pathogenic	-0.373	Destabilizing	0.903	D	0.535	neutral	None	None	None	None	I
V/L	0.2694	likely_benign	0.3243	benign	-0.272	Destabilizing	0.128	N	0.417	neutral	N	0.440168026	None	None	I
V/M	0.1581	likely_benign	0.1947	benign	-0.466	Destabilizing	0.989	D	0.446	neutral	None	None	None	None	I
V/N	0.2914	likely_benign	0.3309	benign	-0.136	Destabilizing	0.736	D	0.615	neutral	None	None	None	None	I
V/P	0.9202	likely_pathogenic	0.9411	pathogenic	-0.254	Destabilizing	0.736	D	0.573	neutral	None	None	None	None	I
V/Q	0.4347	ambiguous	0.4779	ambiguous	-0.377	Destabilizing	0.93	D	0.601	neutral	None	None	None	None	I
V/R	0.469	ambiguous	0.5297	ambiguous	0.118	Stabilizing	0.976	D	0.611	neutral	None	None	None	None	I
V/S	0.1708	likely_benign	0.2149	benign	-0.436	Destabilizing	0.604	D	0.523	neutral	None	None	None	None	I
V/T	0.1697	likely_benign	0.2056	benign	-0.469	Destabilizing	0.551	D	0.375	neutral	None	None	None	None	I
V/W	0.8264	likely_pathogenic	0.8655	pathogenic	-0.751	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	I
V/Y	0.4908	ambiguous	0.568	pathogenic	-0.462	Destabilizing	0.992	D	0.486	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.