TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22173	66742;66743;66744	chr2:178581751;178581750;178581749	chr2:179446478;179446477;179446476
N2AB	20532	61819;61820;61821	chr2:178581751;178581750;178581749	chr2:179446478;179446477;179446476
N2A	19605	59038;59039;59040	chr2:178581751;178581750;178581749	chr2:179446478;179446477;179446476
N2B	13108	39547;39548;39549	chr2:178581751;178581750;178581749	chr2:179446478;179446477;179446476
Novex-1	13233	39922;39923;39924	chr2:178581751;178581750;178581749	chr2:179446478;179446477;179446476
Novex-2	13300	40123;40124;40125	chr2:178581751;178581750;178581749	chr2:179446478;179446477;179446476
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: Fn3-49
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.1298
• 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/A	rs746199327	-2.496	0.656	N	0.632	0.311	0.507748507896	gnomAD-2.1.1	4.2E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.34E-06	0
V/A	rs746199327	-2.496	0.656	N	0.632	0.311	0.507748507896	gnomAD-4.0.0	1.60731E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88452E-06	0	0
V/L	rs1347199587	-0.343	0.125	N	0.382	0.096	0.239901079897	gnomAD-2.1.1	4.21E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.36E-06	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	0.6093	likely_pathogenic	0.5918	pathogenic	-2.257	Highly Destabilizing	0.656	D	0.632	neutral	N	0.504264285	None	None	N
V/C	0.8741	likely_pathogenic	0.8677	pathogenic	-2.526	Highly Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
V/D	0.9954	likely_pathogenic	0.9952	pathogenic	-3.173	Highly Destabilizing	0.993	D	0.871	deleterious	None	None	None	None	N
V/E	0.9866	likely_pathogenic	0.9871	pathogenic	-2.898	Highly Destabilizing	0.99	D	0.862	deleterious	D	0.529625704	None	None	N
V/F	0.7155	likely_pathogenic	0.6968	pathogenic	-1.329	Destabilizing	0.956	D	0.837	deleterious	None	None	None	None	N
V/G	0.8979	likely_pathogenic	0.8922	pathogenic	-2.837	Highly Destabilizing	0.97	D	0.87	deleterious	D	0.528611746	None	None	N
V/H	0.9937	likely_pathogenic	0.9939	pathogenic	-2.632	Highly Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
V/I	0.0785	likely_benign	0.079	benign	-0.599	Destabilizing	0.008	N	0.197	neutral	None	None	None	None	N
V/K	0.99	likely_pathogenic	0.9901	pathogenic	-1.821	Destabilizing	0.978	D	0.862	deleterious	None	None	None	None	N
V/L	0.4519	ambiguous	0.4469	ambiguous	-0.599	Destabilizing	0.125	N	0.382	neutral	N	0.514955707	None	None	N
V/M	0.4437	ambiguous	0.4339	ambiguous	-1.194	Destabilizing	0.942	D	0.681	prob.neutral	N	0.491389278	None	None	N
V/N	0.9785	likely_pathogenic	0.979	pathogenic	-2.399	Highly Destabilizing	0.993	D	0.866	deleterious	None	None	None	None	N
V/P	0.994	likely_pathogenic	0.9938	pathogenic	-1.129	Destabilizing	0.993	D	0.834	deleterious	None	None	None	None	N
V/Q	0.9802	likely_pathogenic	0.9812	pathogenic	-2.137	Highly Destabilizing	0.993	D	0.842	deleterious	None	None	None	None	N
V/R	0.9794	likely_pathogenic	0.98	pathogenic	-1.823	Destabilizing	0.993	D	0.868	deleterious	None	None	None	None	N
V/S	0.893	likely_pathogenic	0.888	pathogenic	-3.017	Highly Destabilizing	0.978	D	0.839	deleterious	None	None	None	None	N
V/T	0.815	likely_pathogenic	0.8091	pathogenic	-2.577	Highly Destabilizing	0.86	D	0.695	prob.neutral	None	None	None	None	N
V/W	0.9952	likely_pathogenic	0.9949	pathogenic	-1.813	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
V/Y	0.9676	likely_pathogenic	0.967	pathogenic	-1.493	Destabilizing	0.978	D	0.82	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.