TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28550	85873;85874;85875	chr2:178560484;178560483;178560482	chr2:179425211;179425210;179425209
N2AB	26909	80950;80951;80952	chr2:178560484;178560483;178560482	chr2:179425211;179425210;179425209
N2A	25982	78169;78170;78171	chr2:178560484;178560483;178560482	chr2:179425211;179425210;179425209
N2B	19485	58678;58679;58680	chr2:178560484;178560483;178560482	chr2:179425211;179425210;179425209
Novex-1	19610	59053;59054;59055	chr2:178560484;178560483;178560482	chr2:179425211;179425210;179425209
Novex-2	19677	59254;59255;59256	chr2:178560484;178560483;178560482	chr2:179425211;179425210;179425209
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: Fn3-96
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4374
• 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/D	rs727505194	-0.017	0.449	N	0.817	0.33	None	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	1.93999E-04	0	None	0	0	None	0	None	0	0	0
V/D	rs727505194	-0.017	0.449	N	0.817	0.33	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
V/D	rs727505194	-0.017	0.449	N	0.817	0.33	None	gnomAD-4.0.0	4.95944E-06	None	None	None	None	I	None	1.0686E-04	0	None	0	0	None	0	0	0	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
V/A	0.1666	likely_benign	0.1565	benign	-0.387	Destabilizing	0.046	N	0.431	neutral	N	0.485923666	None	None	I
V/C	0.6447	likely_pathogenic	0.6407	pathogenic	-0.614	Destabilizing	0.892	D	0.549	neutral	None	None	None	None	I
V/D	0.4719	ambiguous	0.4308	ambiguous	0.018	Stabilizing	0.449	N	0.817	deleterious	N	0.509121004	None	None	I
V/E	0.296	likely_benign	0.2764	benign	-0.098	Destabilizing	0.519	D	0.784	deleterious	None	None	None	None	I
V/F	0.2085	likely_benign	0.2005	benign	-0.804	Destabilizing	0.449	N	0.537	neutral	N	0.476431213	None	None	I
V/G	0.2923	likely_benign	0.2694	benign	-0.477	Destabilizing	0.449	N	0.709	prob.delet.	N	0.497511209	None	None	I
V/H	0.551	ambiguous	0.5073	ambiguous	-0.174	Destabilizing	0.962	D	0.797	deleterious	None	None	None	None	I
V/I	0.0762	likely_benign	0.0761	benign	-0.305	Destabilizing	0.001	N	0.15	neutral	N	0.492350993	None	None	I
V/K	0.2599	likely_benign	0.2446	benign	-0.061	Destabilizing	0.519	D	0.783	deleterious	None	None	None	None	I
V/L	0.1581	likely_benign	0.1526	benign	-0.305	Destabilizing	0.016	N	0.427	neutral	N	0.481901926	None	None	I
V/M	0.1401	likely_benign	0.1349	benign	-0.222	Destabilizing	0.519	D	0.504	neutral	None	None	None	None	I
V/N	0.3223	likely_benign	0.28	benign	0.106	Stabilizing	0.519	D	0.811	deleterious	None	None	None	None	I
V/P	0.249	likely_benign	0.2444	benign	-0.3	Destabilizing	0.687	D	0.819	deleterious	None	None	None	None	I
V/Q	0.2841	likely_benign	0.2571	benign	-0.157	Destabilizing	0.687	D	0.8	deleterious	None	None	None	None	I
V/R	0.2403	likely_benign	0.2155	benign	0.336	Stabilizing	0.519	D	0.824	deleterious	None	None	None	None	I
V/S	0.2299	likely_benign	0.2102	benign	-0.28	Destabilizing	0.351	N	0.527	neutral	None	None	None	None	I
V/T	0.1675	likely_benign	0.1595	benign	-0.299	Destabilizing	0.001	N	0.292	neutral	None	None	None	None	I
V/W	0.8112	likely_pathogenic	0.7987	pathogenic	-0.852	Destabilizing	0.962	D	0.76	deleterious	None	None	None	None	I
V/Y	0.5228	ambiguous	0.5013	ambiguous	-0.498	Destabilizing	0.687	D	0.485	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.