TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6354	19285;19286;19287	chr2:178728978;178728977;178728976	chr2:179593705;179593704;179593703
N2AB	6037	18334;18335;18336	chr2:178728978;178728977;178728976	chr2:179593705;179593704;179593703
N2A	5110	15553;15554;15555	chr2:178728978;178728977;178728976	chr2:179593705;179593704;179593703
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-47
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.076
• 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/M	rs754383943	-1.602	0.998	D	0.564	0.495	0.668719517119	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/M	rs754383943	-1.602	0.998	D	0.564	0.495	0.668719517119	gnomAD-4.0.0	6.57358E-06	None	None	None	None	N	None	2.41348E-05	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	0.2215	likely_benign	0.1962	benign	-1.907	Destabilizing	0.91	D	0.459	neutral	N	0.468221419	None	None	N
V/C	0.8791	likely_pathogenic	0.8672	pathogenic	-2.555	Highly Destabilizing	0.092	N	0.393	neutral	None	None	None	None	N
V/D	0.9487	likely_pathogenic	0.9466	pathogenic	-3.039	Highly Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
V/E	0.9146	likely_pathogenic	0.9118	pathogenic	-2.941	Highly Destabilizing	0.998	D	0.639	neutral	D	0.558058394	None	None	N
V/F	0.6508	likely_pathogenic	0.6813	pathogenic	-1.547	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
V/G	0.5551	ambiguous	0.5616	ambiguous	-2.261	Highly Destabilizing	0.994	D	0.669	neutral	D	0.558058394	None	None	N
V/H	0.9745	likely_pathogenic	0.9745	pathogenic	-1.716	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	N
V/I	0.0927	likely_benign	0.085	benign	-0.971	Destabilizing	0.965	D	0.522	neutral	None	None	None	None	N
V/K	0.9484	likely_pathogenic	0.9494	pathogenic	-1.778	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
V/L	0.443	ambiguous	0.3968	ambiguous	-0.971	Destabilizing	0.91	D	0.472	neutral	N	0.514073926	None	None	N
V/M	0.3432	ambiguous	0.3184	benign	-1.343	Destabilizing	0.998	D	0.564	neutral	D	0.53944716	None	None	N
V/N	0.865	likely_pathogenic	0.8476	pathogenic	-2.077	Highly Destabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	N
V/P	0.82	likely_pathogenic	0.8618	pathogenic	-1.257	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
V/Q	0.9218	likely_pathogenic	0.9209	pathogenic	-2.189	Highly Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
V/R	0.9183	likely_pathogenic	0.9244	pathogenic	-1.34	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
V/S	0.5259	ambiguous	0.4814	ambiguous	-2.586	Highly Destabilizing	0.985	D	0.62	neutral	None	None	None	None	N
V/T	0.2844	likely_benign	0.2457	benign	-2.371	Highly Destabilizing	0.985	D	0.555	neutral	None	None	None	None	N
V/W	0.9868	likely_pathogenic	0.9883	pathogenic	-1.808	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
V/Y	0.9634	likely_pathogenic	0.9666	pathogenic	-1.475	Destabilizing	0.999	D	0.629	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.