TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33507	100744;100745;100746	chr2:178536228;178536227;178536226	chr2:179400955;179400954;179400953
N2AB	31866	95821;95822;95823	chr2:178536228;178536227;178536226	chr2:179400955;179400954;179400953
N2A	30939	93040;93041;93042	chr2:178536228;178536227;178536226	chr2:179400955;179400954;179400953
N2B	24442	73549;73550;73551	chr2:178536228;178536227;178536226	chr2:179400955;179400954;179400953
Novex-1	24567	73924;73925;73926	chr2:178536228;178536227;178536226	chr2:179400955;179400954;179400953
Novex-2	24634	74125;74126;74127	chr2:178536228;178536227;178536226	chr2:179400955;179400954;179400953
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-158
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1576
• 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	0.42	N	0.281	0.211	0.539656846532	gnomAD-4.0.0	3.18523E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86038E-06	1.4341E-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	0.5979	likely_pathogenic	0.5127	ambiguous	-1.804	Destabilizing	0.999	D	0.441	neutral	N	0.471301796	None	None	N
V/C	0.9078	likely_pathogenic	0.888	pathogenic	-1.477	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
V/D	0.9934	likely_pathogenic	0.989	pathogenic	-1.93	Destabilizing	1.0	D	0.719	prob.delet.	D	0.546132658	None	None	N
V/E	0.9818	likely_pathogenic	0.968	pathogenic	-1.878	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	N
V/F	0.8716	likely_pathogenic	0.807	pathogenic	-1.361	Destabilizing	1.0	D	0.685	prob.neutral	N	0.504555323	None	None	N
V/G	0.8212	likely_pathogenic	0.7538	pathogenic	-2.175	Highly Destabilizing	1.0	D	0.707	prob.neutral	N	0.500035873	None	None	N
V/H	0.9936	likely_pathogenic	0.9895	pathogenic	-1.707	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
V/I	0.1705	likely_benign	0.1399	benign	-0.853	Destabilizing	0.42	N	0.281	neutral	N	0.521114541	None	None	N
V/K	0.9845	likely_pathogenic	0.9688	pathogenic	-1.425	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
V/L	0.7983	likely_pathogenic	0.6917	pathogenic	-0.853	Destabilizing	0.918	D	0.437	neutral	D	0.523770844	None	None	N
V/M	0.737	likely_pathogenic	0.6414	pathogenic	-0.813	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
V/N	0.9759	likely_pathogenic	0.9566	pathogenic	-1.37	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
V/P	0.9939	likely_pathogenic	0.9909	pathogenic	-1.138	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
V/Q	0.9685	likely_pathogenic	0.9462	pathogenic	-1.502	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
V/R	0.9745	likely_pathogenic	0.9584	pathogenic	-0.975	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
V/S	0.849	likely_pathogenic	0.7873	pathogenic	-1.948	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
V/T	0.665	likely_pathogenic	0.5355	ambiguous	-1.78	Destabilizing	0.997	D	0.669	neutral	None	None	None	None	N
V/W	0.9987	likely_pathogenic	0.9979	pathogenic	-1.598	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
V/Y	0.99	likely_pathogenic	0.9828	pathogenic	-1.284	Destabilizing	1.0	D	0.701	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.