TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2848	8767;8768;8769	chr2:178770159;178770158;178770157	chr2:179634886;179634885;179634884
N2AB	2848	8767;8768;8769	chr2:178770159;178770158;178770157	chr2:179634886;179634885;179634884
N2A	2848	8767;8768;8769	chr2:178770159;178770158;178770157	chr2:179634886;179634885;179634884
N2B	2802	8629;8630;8631	chr2:178770159;178770158;178770157	chr2:179634886;179634885;179634884
Novex-1	2802	8629;8630;8631	chr2:178770159;178770158;178770157	chr2:179634886;179634885;179634884
Novex-2	2802	8629;8630;8631	chr2:178770159;178770158;178770157	chr2:179634886;179634885;179634884
Novex-3	2848	8767;8768;8769	chr2:178770159;178770158;178770157	chr2:179634886;179634885;179634884

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-18
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.1874
• 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	None	None	0.835	N	0.498	0.231	0.454987352986	gnomAD-4.0.0	1.59046E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02133E-05

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	0.5206	ambiguous	0.5077	ambiguous	-1.858	Destabilizing	0.122	N	0.216	neutral	N	0.4866082	None	None	N
V/C	0.9022	likely_pathogenic	0.9171	pathogenic	-1.255	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
V/D	0.8799	likely_pathogenic	0.8589	pathogenic	-2.247	Highly Destabilizing	0.994	D	0.784	deleterious	N	0.503775787	None	None	N
V/E	0.7397	likely_pathogenic	0.7279	pathogenic	-2.207	Highly Destabilizing	0.996	D	0.725	prob.delet.	None	None	None	None	N
V/F	0.4224	ambiguous	0.4299	ambiguous	-1.343	Destabilizing	0.994	D	0.753	deleterious	N	0.512652949	None	None	N
V/G	0.5676	likely_pathogenic	0.5513	ambiguous	-2.215	Highly Destabilizing	0.925	D	0.721	prob.delet.	N	0.507473517	None	None	N
V/H	0.8714	likely_pathogenic	0.8718	pathogenic	-1.777	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
V/I	0.0987	likely_benign	0.1126	benign	-0.94	Destabilizing	0.248	N	0.24	neutral	N	0.506099526	None	None	N
V/K	0.7928	likely_pathogenic	0.7852	pathogenic	-1.587	Destabilizing	0.991	D	0.724	prob.delet.	None	None	None	None	N
V/L	0.4364	ambiguous	0.5085	ambiguous	-0.94	Destabilizing	0.835	D	0.498	neutral	N	0.494356381	None	None	N
V/M	0.2694	likely_benign	0.3182	benign	-0.718	Destabilizing	0.996	D	0.658	neutral	None	None	None	None	N
V/N	0.6247	likely_pathogenic	0.6238	pathogenic	-1.479	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
V/P	0.9945	likely_pathogenic	0.9901	pathogenic	-1.215	Destabilizing	0.996	D	0.755	deleterious	None	None	None	None	N
V/Q	0.6528	likely_pathogenic	0.6503	pathogenic	-1.63	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
V/R	0.7673	likely_pathogenic	0.7357	pathogenic	-1.045	Destabilizing	0.996	D	0.796	deleterious	None	None	None	None	N
V/S	0.5606	ambiguous	0.5598	ambiguous	-1.969	Destabilizing	0.942	D	0.697	prob.neutral	None	None	None	None	N
V/T	0.4116	ambiguous	0.4454	ambiguous	-1.83	Destabilizing	0.97	D	0.587	neutral	None	None	None	None	N
V/W	0.9594	likely_pathogenic	0.9575	pathogenic	-1.635	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
V/Y	0.8077	likely_pathogenic	0.8073	pathogenic	-1.361	Destabilizing	0.999	D	0.749	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.