TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14226	42901;42902;42903	chr2:178633823;178633822;178633821	chr2:179498550;179498549;179498548
N2AB	12585	37978;37979;37980	chr2:178633823;178633822;178633821	chr2:179498550;179498549;179498548
N2A	11658	35197;35198;35199	chr2:178633823;178633822;178633821	chr2:179498550;179498549;179498548
N2B	5161	15706;15707;15708	chr2:178633823;178633822;178633821	chr2:179498550;179498549;179498548
Novex-1	5286	16081;16082;16083	chr2:178633823;178633822;178633821	chr2:179498550;179498549;179498548
Novex-2	5353	16282;16283;16284	chr2:178633823;178633822;178633821	chr2:179498550;179498549;179498548
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-92
• Domain position: 85
• Structural Position: 178
• Q(SASA): 0.3315
• 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	rs1232583484	-0.464	0.997	D	0.467	0.359	0.736372478493	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
V/I	rs1232583484	-0.464	0.997	D	0.467	0.359	0.736372478493	gnomAD-4.0.0	1.59314E-06	None	None	None	None	N	None	0	2.28833E-05	None	0	0	None	0	0	0	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	0.9191	likely_pathogenic	0.918	pathogenic	-1.871	Destabilizing	0.999	D	0.544	neutral	D	0.692007785	None	None	N
V/C	0.986	likely_pathogenic	0.9854	pathogenic	-1.356	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
V/D	0.9935	likely_pathogenic	0.995	pathogenic	-2.111	Highly Destabilizing	1.0	D	0.739	prob.delet.	D	0.694258001	None	None	N
V/E	0.9854	likely_pathogenic	0.9881	pathogenic	-1.964	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
V/F	0.9578	likely_pathogenic	0.9546	pathogenic	-1.1	Destabilizing	1.0	D	0.709	prob.delet.	D	0.693528098	None	None	N
V/G	0.8948	likely_pathogenic	0.8989	pathogenic	-2.327	Highly Destabilizing	1.0	D	0.714	prob.delet.	D	0.694258001	None	None	N
V/H	0.9976	likely_pathogenic	0.9976	pathogenic	-1.978	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
V/I	0.2344	likely_benign	0.2228	benign	-0.637	Destabilizing	0.997	D	0.467	neutral	D	0.569889944	None	None	N
V/K	0.9895	likely_pathogenic	0.9909	pathogenic	-1.525	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
V/L	0.9033	likely_pathogenic	0.8903	pathogenic	-0.637	Destabilizing	0.997	D	0.526	neutral	D	0.689842966	None	None	N
V/M	0.9425	likely_pathogenic	0.933	pathogenic	-0.67	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
V/N	0.9824	likely_pathogenic	0.9834	pathogenic	-1.629	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
V/P	0.9869	likely_pathogenic	0.9867	pathogenic	-1.019	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
V/Q	0.9916	likely_pathogenic	0.9926	pathogenic	-1.584	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
V/R	0.984	likely_pathogenic	0.9861	pathogenic	-1.251	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
V/S	0.9685	likely_pathogenic	0.9677	pathogenic	-2.236	Highly Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
V/T	0.9374	likely_pathogenic	0.9321	pathogenic	-1.967	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
V/W	0.9994	likely_pathogenic	0.9993	pathogenic	-1.517	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
V/Y	0.9925	likely_pathogenic	0.9924	pathogenic	-1.164	Destabilizing	1.0	D	0.719	prob.delet.	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.