TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18158	54697;54698;54699	chr2:178604215;178604214;178604213	chr2:179468942;179468941;179468940
N2AB	16517	49774;49775;49776	chr2:178604215;178604214;178604213	chr2:179468942;179468941;179468940
N2A	15590	46993;46994;46995	chr2:178604215;178604214;178604213	chr2:179468942;179468941;179468940
N2B	9093	27502;27503;27504	chr2:178604215;178604214;178604213	chr2:179468942;179468941;179468940
Novex-1	9218	27877;27878;27879	chr2:178604215;178604214;178604213	chr2:179468942;179468941;179468940
Novex-2	9285	28078;28079;28080	chr2:178604215;178604214;178604213	chr2:179468942;179468941;179468940
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-19
• Domain position: 94
• Structural Position: 127
• Q(SASA): 0.3069
• 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
V/I	None	None	0.003	N	0.284	0.064	0.329282125956	gnomAD-4.0.0	1.37133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.8014E-06	0	0
V/L	None	None	0.046	N	0.412	0.123	0.435915822735	gnomAD-4.0.0	6.85663E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16632E-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
V/A	0.3074	likely_benign	0.253	benign	-1.541	Destabilizing	0.046	N	0.431	neutral	N	0.472076347	None	None	N
V/C	0.8442	likely_pathogenic	0.8369	pathogenic	-1.149	Destabilizing	0.892	D	0.693	prob.delet.	None	None	None	None	N
V/D	0.8876	likely_pathogenic	0.8567	pathogenic	-1.728	Destabilizing	0.519	D	0.862	deleterious	None	None	None	None	N
V/E	0.7218	likely_pathogenic	0.648	pathogenic	-1.566	Destabilizing	0.449	N	0.793	deleterious	N	0.496056405	None	None	N
V/F	0.4275	ambiguous	0.3465	ambiguous	-0.846	Destabilizing	0.687	D	0.678	prob.neutral	None	None	None	None	N
V/G	0.6229	likely_pathogenic	0.5808	pathogenic	-2.005	Highly Destabilizing	0.449	N	0.792	deleterious	N	0.496563384	None	None	N
V/H	0.8666	likely_pathogenic	0.8362	pathogenic	-1.534	Destabilizing	0.962	D	0.829	deleterious	None	None	None	None	N
V/I	0.0895	likely_benign	0.0838	benign	-0.296	Destabilizing	0.003	N	0.284	neutral	N	0.482499359	None	None	N
V/K	0.726	likely_pathogenic	0.6756	pathogenic	-1.457	Destabilizing	0.519	D	0.794	deleterious	None	None	None	None	N
V/L	0.4049	ambiguous	0.3722	ambiguous	-0.296	Destabilizing	0.046	N	0.412	neutral	N	0.463046991	None	None	N
V/M	0.2732	likely_benign	0.2207	benign	-0.328	Destabilizing	0.687	D	0.533	neutral	None	None	None	None	N
V/N	0.7485	likely_pathogenic	0.7237	pathogenic	-1.682	Destabilizing	0.519	D	0.869	deleterious	None	None	None	None	N
V/P	0.9608	likely_pathogenic	0.9641	pathogenic	-0.68	Destabilizing	0.687	D	0.811	deleterious	None	None	None	None	N
V/Q	0.6913	likely_pathogenic	0.6357	pathogenic	-1.588	Destabilizing	0.687	D	0.823	deleterious	None	None	None	None	N
V/R	0.7166	likely_pathogenic	0.6624	pathogenic	-1.193	Destabilizing	0.519	D	0.873	deleterious	None	None	None	None	N
V/S	0.5904	likely_pathogenic	0.5314	ambiguous	-2.271	Highly Destabilizing	0.351	N	0.743	deleterious	None	None	None	None	N
V/T	0.2325	likely_benign	0.194	benign	-1.966	Destabilizing	0.001	N	0.339	neutral	None	None	None	None	N
V/W	0.9537	likely_pathogenic	0.9328	pathogenic	-1.248	Destabilizing	0.962	D	0.769	deleterious	None	None	None	None	N
V/Y	0.8335	likely_pathogenic	0.782	pathogenic	-0.842	Destabilizing	0.687	D	0.674	prob.neutral	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.