TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13792	41599;41600;41601	chr2:178636197;178636196;178636195	chr2:179500924;179500923;179500922
N2AB	12151	36676;36677;36678	chr2:178636197;178636196;178636195	chr2:179500924;179500923;179500922
N2A	11224	33895;33896;33897	chr2:178636197;178636196;178636195	chr2:179500924;179500923;179500922
N2B	4727	14404;14405;14406	chr2:178636197;178636196;178636195	chr2:179500924;179500923;179500922
Novex-1	4852	14779;14780;14781	chr2:178636197;178636196;178636195	chr2:179500924;179500923;179500922
Novex-2	4919	14980;14981;14982	chr2:178636197;178636196;178636195	chr2:179500924;179500923;179500922
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-88
• Domain position: 13
• Structural Position: 16
• Q(SASA): 0.3514
• 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	rs1445036438	None	0.999	N	0.405	0.333	0.42264334713	gnomAD-4.0.0	2.06631E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.71256E-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	0.6195	likely_pathogenic	0.6463	pathogenic	-1.561	Destabilizing	0.219	N	0.202	neutral	N	0.345435064	None	None	N
V/C	0.9485	likely_pathogenic	0.942	pathogenic	-1.056	Destabilizing	1.0	D	0.479	neutral	None	None	None	None	N
V/D	0.9906	likely_pathogenic	0.9904	pathogenic	-1.561	Destabilizing	0.998	D	0.669	prob.neutral	None	None	None	None	N
V/E	0.9699	likely_pathogenic	0.9699	pathogenic	-1.544	Destabilizing	0.997	D	0.545	neutral	N	0.491508095	None	None	N
V/F	0.8563	likely_pathogenic	0.8542	pathogenic	-1.149	Destabilizing	0.999	D	0.425	neutral	None	None	None	None	N
V/G	0.8405	likely_pathogenic	0.853	pathogenic	-1.899	Destabilizing	0.98	D	0.625	neutral	N	0.432703853	None	None	N
V/H	0.9926	likely_pathogenic	0.9918	pathogenic	-1.52	Destabilizing	1.0	D	0.687	prob.delet.	None	None	None	None	N
V/I	0.1656	likely_benign	0.1702	benign	-0.72	Destabilizing	0.985	D	0.497	neutral	None	None	None	None	N
V/K	0.9759	likely_pathogenic	0.9756	pathogenic	-1.389	Destabilizing	0.998	D	0.541	neutral	None	None	None	None	N
V/L	0.7761	likely_pathogenic	0.7898	pathogenic	-0.72	Destabilizing	0.953	D	0.473	neutral	N	0.377821107	None	None	N
V/M	0.6879	likely_pathogenic	0.6852	pathogenic	-0.569	Destabilizing	0.999	D	0.405	neutral	N	0.455558689	None	None	N
V/N	0.9692	likely_pathogenic	0.9698	pathogenic	-1.2	Destabilizing	0.998	D	0.687	prob.delet.	None	None	None	None	N
V/P	0.9914	likely_pathogenic	0.9891	pathogenic	-0.966	Destabilizing	0.998	D	0.613	neutral	None	None	None	None	N
V/Q	0.9622	likely_pathogenic	0.9587	pathogenic	-1.347	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
V/R	0.9577	likely_pathogenic	0.9572	pathogenic	-0.897	Destabilizing	0.998	D	0.687	prob.delet.	None	None	None	None	N
V/S	0.863	likely_pathogenic	0.8701	pathogenic	-1.704	Destabilizing	0.971	D	0.555	neutral	None	None	None	None	N
V/T	0.6773	likely_pathogenic	0.69	pathogenic	-1.582	Destabilizing	0.469	N	0.312	neutral	None	None	None	None	N
V/W	0.9976	likely_pathogenic	0.9972	pathogenic	-1.392	Destabilizing	1.0	D	0.656	prob.neutral	None	None	None	None	N
V/Y	0.987	likely_pathogenic	0.9857	pathogenic	-1.098	Destabilizing	0.999	D	0.433	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.