TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15061	45406;45407;45408	chr2:178621643;178621642;178621641	chr2:179486370;179486369;179486368
N2AB	13420	40483;40484;40485	chr2:178621643;178621642;178621641	chr2:179486370;179486369;179486368
N2A	12493	37702;37703;37704	chr2:178621643;178621642;178621641	chr2:179486370;179486369;179486368
N2B	5996	18211;18212;18213	chr2:178621643;178621642;178621641	chr2:179486370;179486369;179486368
Novex-1	6121	18586;18587;18588	chr2:178621643;178621642;178621641	chr2:179486370;179486369;179486368
Novex-2	6188	18787;18788;18789	chr2:178621643;178621642;178621641	chr2:179486370;179486369;179486368
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-102
• Domain position: 31
• Structural Position: 46
• Q(SASA): 0.1958
• 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/G	None	None	1.0	D	0.837	0.744	0.941024214575	gnomAD-4.0.0	1.5938E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86269E-06	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	0.4492	ambiguous	0.4257	ambiguous	-1.676	Destabilizing	0.999	D	0.587	neutral	D	0.745981034	None	None	N
V/C	0.9153	likely_pathogenic	0.9308	pathogenic	-0.98	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/D	0.9487	likely_pathogenic	0.935	pathogenic	-2.064	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
V/E	0.9236	likely_pathogenic	0.9115	pathogenic	-1.915	Destabilizing	1.0	D	0.83	deleterious	D	0.835632846	None	None	N
V/F	0.6706	likely_pathogenic	0.7039	pathogenic	-1.056	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
V/G	0.5176	ambiguous	0.5155	ambiguous	-2.108	Highly Destabilizing	1.0	D	0.837	deleterious	D	0.766196861	None	None	N
V/H	0.9866	likely_pathogenic	0.9857	pathogenic	-1.638	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/I	0.1297	likely_benign	0.1386	benign	-0.511	Destabilizing	0.998	D	0.557	neutral	None	None	None	None	N
V/K	0.9701	likely_pathogenic	0.9687	pathogenic	-1.414	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/L	0.5814	likely_pathogenic	0.6344	pathogenic	-0.511	Destabilizing	0.997	D	0.607	neutral	D	0.649125915	None	None	N
V/M	0.477	ambiguous	0.4823	ambiguous	-0.406	Destabilizing	1.0	D	0.741	deleterious	D	0.729914968	None	None	N
V/N	0.8948	likely_pathogenic	0.889	pathogenic	-1.545	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/P	0.8425	likely_pathogenic	0.8971	pathogenic	-0.87	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
V/Q	0.9559	likely_pathogenic	0.9533	pathogenic	-1.525	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/R	0.9606	likely_pathogenic	0.961	pathogenic	-1.094	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/S	0.7477	likely_pathogenic	0.7407	pathogenic	-2.071	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/T	0.5756	likely_pathogenic	0.5706	pathogenic	-1.795	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
V/W	0.99	likely_pathogenic	0.9921	pathogenic	-1.448	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
V/Y	0.9504	likely_pathogenic	0.9574	pathogenic	-1.05	Destabilizing	1.0	D	0.787	deleterious	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.