TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33613	101062;101063;101064	chr2:178535778;178535777;178535776	chr2:179400505;179400504;179400503
N2AB	31972	96139;96140;96141	chr2:178535778;178535777;178535776	chr2:179400505;179400504;179400503
N2A	31045	93358;93359;93360	chr2:178535778;178535777;178535776	chr2:179400505;179400504;179400503
N2B	24548	73867;73868;73869	chr2:178535778;178535777;178535776	chr2:179400505;179400504;179400503
Novex-1	24673	74242;74243;74244	chr2:178535778;178535777;178535776	chr2:179400505;179400504;179400503
Novex-2	24740	74443;74444;74445	chr2:178535778;178535777;178535776	chr2:179400505;179400504;179400503
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-159
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1102
• 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/G	None	None	0.942	N	0.829	0.473	0.685509544888	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/I	rs1691163067	None	None	N	0.199	0.143	0.154104182512	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs1691163067	None	None	N	0.199	0.143	0.154104182512	gnomAD-4.0.0	2.56487E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78696E-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	0.7098	likely_pathogenic	0.4934	ambiguous	-1.456	Destabilizing	0.219	N	0.557	neutral	N	0.46207844	None	None	N
V/C	0.9087	likely_pathogenic	0.8284	pathogenic	-1.206	Destabilizing	0.987	D	0.73	prob.delet.	None	None	None	None	N
V/D	0.9816	likely_pathogenic	0.9489	pathogenic	-1.219	Destabilizing	0.922	D	0.833	deleterious	N	0.486009411	None	None	N
V/E	0.9464	likely_pathogenic	0.8828	pathogenic	-1.072	Destabilizing	0.719	D	0.813	deleterious	None	None	None	None	N
V/F	0.6875	likely_pathogenic	0.3907	ambiguous	-0.768	Destabilizing	0.816	D	0.818	deleterious	N	0.461775863	None	None	N
V/G	0.8953	likely_pathogenic	0.7756	pathogenic	-1.916	Destabilizing	0.942	D	0.829	deleterious	N	0.462789821	None	None	N
V/H	0.9714	likely_pathogenic	0.9196	pathogenic	-1.392	Destabilizing	0.99	D	0.799	deleterious	None	None	None	None	N
V/I	0.087	likely_benign	0.0752	benign	-0.236	Destabilizing	None	N	0.199	neutral	N	0.456192618	None	None	N
V/K	0.9258	likely_pathogenic	0.8379	pathogenic	-1.237	Destabilizing	0.848	D	0.816	deleterious	None	None	None	None	N
V/L	0.3589	ambiguous	0.2054	benign	-0.236	Destabilizing	0.003	N	0.393	neutral	N	0.437297426	None	None	N
V/M	0.495	ambiguous	0.2707	benign	-0.385	Destabilizing	0.808	D	0.669	neutral	None	None	None	None	N
V/N	0.9354	likely_pathogenic	0.8335	pathogenic	-1.396	Destabilizing	0.716	D	0.831	deleterious	None	None	None	None	N
V/P	0.984	likely_pathogenic	0.9587	pathogenic	-0.61	Destabilizing	0.716	D	0.789	deleterious	None	None	None	None	N
V/Q	0.918	likely_pathogenic	0.8197	pathogenic	-1.301	Destabilizing	0.923	D	0.797	deleterious	None	None	None	None	N
V/R	0.8977	likely_pathogenic	0.8015	pathogenic	-1.013	Destabilizing	0.922	D	0.831	deleterious	None	None	None	None	N
V/S	0.8921	likely_pathogenic	0.7493	pathogenic	-2.063	Highly Destabilizing	0.865	D	0.803	deleterious	None	None	None	None	N
V/T	0.6787	likely_pathogenic	0.4999	ambiguous	-1.763	Destabilizing	0.267	N	0.631	neutral	None	None	None	None	N
V/W	0.9901	likely_pathogenic	0.9651	pathogenic	-1.091	Destabilizing	0.997	D	0.768	deleterious	None	None	None	None	N
V/Y	0.9588	likely_pathogenic	0.8686	pathogenic	-0.709	Destabilizing	0.922	D	0.791	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.