TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13710	41353;41354;41355	chr2:178636599;178636598;178636597	chr2:179501326;179501325;179501324
N2AB	12069	36430;36431;36432	chr2:178636599;178636598;178636597	chr2:179501326;179501325;179501324
N2A	11142	33649;33650;33651	chr2:178636599;178636598;178636597	chr2:179501326;179501325;179501324
N2B	4645	14158;14159;14160	chr2:178636599;178636598;178636597	chr2:179501326;179501325;179501324
Novex-1	4770	14533;14534;14535	chr2:178636599;178636598;178636597	chr2:179501326;179501325;179501324
Novex-2	4837	14734;14735;14736	chr2:178636599;178636598;178636597	chr2:179501326;179501325;179501324
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: Ig-87
• Domain position: 27
• Structural Position: 35
• Q(SASA): 0.1081
• 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/I	rs1429685157	-0.915	0.046	D	0.205	0.161	0.507628581994	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/I	rs1429685157	-0.915	0.046	D	0.205	0.161	0.507628581994	gnomAD-4.0.0	3.18402E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86574E-05	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	0.9142	likely_pathogenic	0.9475	pathogenic	-2.243	Highly Destabilizing	0.939	D	0.564	neutral	D	0.530033848	None	None	N
V/C	0.9795	likely_pathogenic	0.9854	pathogenic	-1.997	Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
V/D	0.9974	likely_pathogenic	0.9986	pathogenic	-3.025	Highly Destabilizing	0.997	D	0.848	deleterious	D	0.741082847	None	None	N
V/E	0.9915	likely_pathogenic	0.9958	pathogenic	-2.821	Highly Destabilizing	0.998	D	0.829	deleterious	None	None	None	None	N
V/F	0.9179	likely_pathogenic	0.9723	pathogenic	-1.319	Destabilizing	0.982	D	0.817	deleterious	D	0.666660349	None	None	N
V/G	0.9565	likely_pathogenic	0.9738	pathogenic	-2.735	Highly Destabilizing	0.997	D	0.831	deleterious	D	0.681881423	None	None	N
V/H	0.9974	likely_pathogenic	0.9988	pathogenic	-2.388	Highly Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
V/I	0.1498	likely_benign	0.1642	benign	-0.865	Destabilizing	0.046	N	0.205	neutral	D	0.528796589	None	None	N
V/K	0.9964	likely_pathogenic	0.9981	pathogenic	-1.764	Destabilizing	0.993	D	0.829	deleterious	None	None	None	None	N
V/L	0.8251	likely_pathogenic	0.8879	pathogenic	-0.865	Destabilizing	0.76	D	0.526	neutral	D	0.537081485	None	None	N
V/M	0.9059	likely_pathogenic	0.9503	pathogenic	-1.114	Destabilizing	0.986	D	0.754	deleterious	None	None	None	None	N
V/N	0.9912	likely_pathogenic	0.9952	pathogenic	-2.12	Highly Destabilizing	0.998	D	0.867	deleterious	None	None	None	None	N
V/P	0.9893	likely_pathogenic	0.9935	pathogenic	-1.3	Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	N
V/Q	0.9911	likely_pathogenic	0.9961	pathogenic	-1.994	Destabilizing	0.998	D	0.851	deleterious	None	None	None	None	N
V/R	0.9917	likely_pathogenic	0.9954	pathogenic	-1.57	Destabilizing	0.998	D	0.864	deleterious	None	None	None	None	N
V/S	0.9642	likely_pathogenic	0.976	pathogenic	-2.688	Highly Destabilizing	0.993	D	0.813	deleterious	None	None	None	None	N
V/T	0.9198	likely_pathogenic	0.9328	pathogenic	-2.354	Highly Destabilizing	0.953	D	0.66	neutral	None	None	None	None	N
V/W	0.9987	likely_pathogenic	0.9995	pathogenic	-1.791	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
V/Y	0.9918	likely_pathogenic	0.997	pathogenic	-1.482	Destabilizing	0.998	D	0.819	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.