TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27010	81253;81254;81255	chr2:178565104;178565103;178565102	chr2:179429831;179429830;179429829
N2AB	25369	76330;76331;76332	chr2:178565104;178565103;178565102	chr2:179429831;179429830;179429829
N2A	24442	73549;73550;73551	chr2:178565104;178565103;178565102	chr2:179429831;179429830;179429829
N2B	17945	54058;54059;54060	chr2:178565104;178565103;178565102	chr2:179429831;179429830;179429829
Novex-1	18070	54433;54434;54435	chr2:178565104;178565103;178565102	chr2:179429831;179429830;179429829
Novex-2	18137	54634;54635;54636	chr2:178565104;178565103;178565102	chr2:179429831;179429830;179429829
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-84
• Domain position: 39
• Structural Position: 40
• Q(SASA): 0.0801
• 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/A	rs369235214	-2.572	0.999	D	0.591	0.641	None	gnomAD-2.1.1	2.42E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	5.34E-05	0
V/A	rs369235214	-2.572	0.999	D	0.591	0.641	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
V/A	rs369235214	-2.572	0.999	D	0.591	0.641	None	gnomAD-4.0.0	2.10731E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.6279E-05	0	4.80415E-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	0.8045	likely_pathogenic	0.768	pathogenic	-2.545	Highly Destabilizing	0.999	D	0.591	neutral	D	0.539337666	None	None	N
V/C	0.9735	likely_pathogenic	0.955	pathogenic	-1.896	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/D	0.9993	likely_pathogenic	0.9995	pathogenic	-3.509	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/E	0.9971	likely_pathogenic	0.9976	pathogenic	-3.165	Highly Destabilizing	1.0	D	0.854	deleterious	D	0.562810745	None	None	N
V/F	0.9326	likely_pathogenic	0.918	pathogenic	-1.472	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
V/G	0.9685	likely_pathogenic	0.9636	pathogenic	-3.176	Highly Destabilizing	1.0	D	0.868	deleterious	D	0.562810745	None	None	N
V/H	0.9992	likely_pathogenic	0.9991	pathogenic	-3.093	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/I	0.0965	likely_benign	0.097	benign	-0.687	Destabilizing	0.997	D	0.565	neutral	N	0.503824354	None	None	N
V/K	0.9979	likely_pathogenic	0.9982	pathogenic	-2.111	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/L	0.5474	ambiguous	0.5112	ambiguous	-0.687	Destabilizing	0.997	D	0.605	neutral	N	0.48361196	None	None	N
V/M	0.7469	likely_pathogenic	0.6731	pathogenic	-0.95	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
V/N	0.9978	likely_pathogenic	0.9977	pathogenic	-2.896	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/P	0.9961	likely_pathogenic	0.9974	pathogenic	-1.291	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/Q	0.9965	likely_pathogenic	0.9966	pathogenic	-2.473	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/R	0.995	likely_pathogenic	0.996	pathogenic	-2.279	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
V/S	0.9783	likely_pathogenic	0.9731	pathogenic	-3.374	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/T	0.8665	likely_pathogenic	0.8463	pathogenic	-2.862	Highly Destabilizing	0.999	D	0.618	neutral	None	None	None	None	N
V/W	0.9992	likely_pathogenic	0.999	pathogenic	-2.014	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/Y	0.9967	likely_pathogenic	0.9959	pathogenic	-1.744	Destabilizing	1.0	D	0.793	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.