TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16787	50584;50585;50586	chr2:178611950;178611949;178611948	chr2:179476677;179476676;179476675
N2AB	15146	45661;45662;45663	chr2:178611950;178611949;178611948	chr2:179476677;179476676;179476675
N2A	14219	42880;42881;42882	chr2:178611950;178611949;178611948	chr2:179476677;179476676;179476675
N2B	7722	23389;23390;23391	chr2:178611950;178611949;178611948	chr2:179476677;179476676;179476675
Novex-1	7847	23764;23765;23766	chr2:178611950;178611949;178611948	chr2:179476677;179476676;179476675
Novex-2	7914	23965;23966;23967	chr2:178611950;178611949;178611948	chr2:179476677;179476676;179476675
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: Fn3-10
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1811
• 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/L	rs1419766789	-0.611	0.009	N	0.551	0.095	0.130388298395	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/L	rs1419766789	-0.611	0.009	N	0.551	0.095	0.130388298395	gnomAD-4.0.0	6.58033E-06	None	None	None	None	N	None	2.41429E-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	0.3965	ambiguous	0.4652	ambiguous	-2.445	Highly Destabilizing	0.027	N	0.608	neutral	N	0.496698461	None	None	N
V/C	0.7388	likely_pathogenic	0.7413	pathogenic	-1.783	Destabilizing	0.935	D	0.682	prob.neutral	None	None	None	None	N
V/D	0.7081	likely_pathogenic	0.7986	pathogenic	-3.126	Highly Destabilizing	0.317	N	0.738	prob.delet.	N	0.469875785	None	None	N
V/E	0.604	likely_pathogenic	0.6883	pathogenic	-2.94	Highly Destabilizing	0.149	N	0.693	prob.neutral	None	None	None	None	N
V/F	0.2244	likely_benign	0.2463	benign	-1.473	Destabilizing	0.317	N	0.719	prob.delet.	N	0.48081517	None	None	N
V/G	0.5675	likely_pathogenic	0.6413	pathogenic	-2.926	Highly Destabilizing	0.117	N	0.707	prob.neutral	D	0.573437653	None	None	N
V/H	0.668	likely_pathogenic	0.7279	pathogenic	-2.563	Highly Destabilizing	0.935	D	0.721	prob.delet.	None	None	None	None	N
V/I	0.0606	likely_benign	0.0583	benign	-1.097	Destabilizing	None	N	0.241	neutral	N	0.430451734	None	None	N
V/K	0.7493	likely_pathogenic	0.7773	pathogenic	-2.19	Highly Destabilizing	0.38	N	0.691	prob.neutral	None	None	None	None	N
V/L	0.187	likely_benign	0.191	benign	-1.097	Destabilizing	0.009	N	0.551	neutral	N	0.472080547	None	None	N
V/M	0.182	likely_benign	0.1878	benign	-1.007	Destabilizing	0.38	N	0.695	prob.neutral	None	None	None	None	N
V/N	0.3924	ambiguous	0.4732	ambiguous	-2.409	Highly Destabilizing	0.38	N	0.727	prob.delet.	None	None	None	None	N
V/P	0.9841	likely_pathogenic	0.9841	pathogenic	-1.523	Destabilizing	0.555	D	0.682	prob.neutral	None	None	None	None	N
V/Q	0.5648	likely_pathogenic	0.6302	pathogenic	-2.323	Highly Destabilizing	0.555	D	0.683	prob.neutral	None	None	None	None	N
V/R	0.6386	likely_pathogenic	0.6834	pathogenic	-1.802	Destabilizing	0.555	D	0.729	prob.delet.	None	None	None	None	N
V/S	0.3463	ambiguous	0.4163	ambiguous	-2.96	Highly Destabilizing	0.007	N	0.507	neutral	None	None	None	None	N
V/T	0.2663	likely_benign	0.3165	benign	-2.662	Highly Destabilizing	0.081	N	0.673	neutral	None	None	None	None	N
V/W	0.8756	likely_pathogenic	0.8926	pathogenic	-1.994	Destabilizing	0.935	D	0.723	prob.delet.	None	None	None	None	N
V/Y	0.6268	likely_pathogenic	0.6432	pathogenic	-1.701	Destabilizing	0.555	D	0.713	prob.delet.	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.