TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15510	46753;46754;46755	chr2:178619789;178619788;178619787	chr2:179484516;179484515;179484514
N2AB	13869	41830;41831;41832	chr2:178619789;178619788;178619787	chr2:179484516;179484515;179484514
N2A	12942	39049;39050;39051	chr2:178619789;178619788;178619787	chr2:179484516;179484515;179484514
N2B	6445	19558;19559;19560	chr2:178619789;178619788;178619787	chr2:179484516;179484515;179484514
Novex-1	6570	19933;19934;19935	chr2:178619789;178619788;178619787	chr2:179484516;179484515;179484514
Novex-2	6637	20134;20135;20136	chr2:178619789;178619788;178619787	chr2:179484516;179484515;179484514
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-107
• Domain position: 31
• Structural Position: 46
• Q(SASA): 0.0819
• 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	rs754751783	-0.295	0.997	D	0.565	0.552	0.643851019634	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
V/L	rs754751783	-0.295	0.997	D	0.565	0.552	0.643851019634	gnomAD-4.0.0	3.18814E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72816E-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	0.4888	ambiguous	0.5945	pathogenic	-1.795	Destabilizing	0.999	D	0.557	neutral	D	0.546790984	None	None	N
V/C	0.8327	likely_pathogenic	0.9268	pathogenic	-1.044	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/D	0.9778	likely_pathogenic	0.9743	pathogenic	-2.214	Highly Destabilizing	1.0	D	0.85	deleterious	D	0.62519196	None	None	N
V/E	0.9602	likely_pathogenic	0.9454	pathogenic	-2.082	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/F	0.7476	likely_pathogenic	0.753	pathogenic	-1.199	Destabilizing	1.0	D	0.825	deleterious	D	0.626695103	None	None	N
V/G	0.6263	likely_pathogenic	0.7064	pathogenic	-2.204	Highly Destabilizing	1.0	D	0.845	deleterious	D	0.547783201	None	None	N
V/H	0.9843	likely_pathogenic	0.9831	pathogenic	-1.74	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/I	0.1524	likely_benign	0.1707	benign	-0.695	Destabilizing	0.997	D	0.506	neutral	N	0.509109617	None	None	N
V/K	0.9612	likely_pathogenic	0.9446	pathogenic	-1.485	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/L	0.7542	likely_pathogenic	0.778	pathogenic	-0.695	Destabilizing	0.997	D	0.565	neutral	D	0.547392255	None	None	N
V/M	0.6366	likely_pathogenic	0.6723	pathogenic	-0.563	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
V/N	0.9163	likely_pathogenic	0.9197	pathogenic	-1.525	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/P	0.8853	likely_pathogenic	0.8448	pathogenic	-1.034	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
V/Q	0.9578	likely_pathogenic	0.9489	pathogenic	-1.551	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/R	0.9523	likely_pathogenic	0.9368	pathogenic	-1.122	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/S	0.7589	likely_pathogenic	0.8035	pathogenic	-2.021	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/T	0.4739	ambiguous	0.5498	ambiguous	-1.77	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
V/W	0.9905	likely_pathogenic	0.9932	pathogenic	-1.549	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/Y	0.9581	likely_pathogenic	0.9606	pathogenic	-1.187	Destabilizing	1.0	D	0.822	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.