TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28840	86743;86744;86745	chr2:178559614;178559613;178559612	chr2:179424341;179424340;179424339
N2AB	27199	81820;81821;81822	chr2:178559614;178559613;178559612	chr2:179424341;179424340;179424339
N2A	26272	79039;79040;79041	chr2:178559614;178559613;178559612	chr2:179424341;179424340;179424339
N2B	19775	59548;59549;59550	chr2:178559614;178559613;178559612	chr2:179424341;179424340;179424339
Novex-1	19900	59923;59924;59925	chr2:178559614;178559613;178559612	chr2:179424341;179424340;179424339
Novex-2	19967	60124;60125;60126	chr2:178559614;178559613;178559612	chr2:179424341;179424340;179424339
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-144
• Domain position: 86
• Structural Position: 174
• Q(SASA): 0.1364
• 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	rs920125248	-1.611	0.999	N	0.613	0.462	0.634904748024	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
V/A	rs920125248	-1.611	0.999	N	0.613	0.462	0.634904748024	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs920125248	-1.611	0.999	N	0.613	0.462	0.634904748024	gnomAD-4.0.0	1.05347E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.44094E-05	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	0.8655	likely_pathogenic	0.8511	pathogenic	-2.018	Highly Destabilizing	0.999	D	0.613	neutral	N	0.506328938	None	None	N
V/C	0.9554	likely_pathogenic	0.9541	pathogenic	-1.526	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
V/D	0.9989	likely_pathogenic	0.9989	pathogenic	-2.823	Highly Destabilizing	1.0	D	0.841	deleterious	N	0.518192223	None	None	N
V/E	0.9962	likely_pathogenic	0.996	pathogenic	-2.537	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
V/F	0.8931	likely_pathogenic	0.869	pathogenic	-1.167	Destabilizing	1.0	D	0.815	deleterious	N	0.516924775	None	None	N
V/G	0.9316	likely_pathogenic	0.9302	pathogenic	-2.623	Highly Destabilizing	1.0	D	0.839	deleterious	N	0.518192223	None	None	N
V/H	0.9987	likely_pathogenic	0.9984	pathogenic	-2.566	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
V/I	0.1332	likely_benign	0.1246	benign	-0.291	Destabilizing	0.997	D	0.557	neutral	N	0.455442306	None	None	N
V/K	0.9964	likely_pathogenic	0.9963	pathogenic	-1.623	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/L	0.6883	likely_pathogenic	0.6599	pathogenic	-0.291	Destabilizing	0.997	D	0.637	neutral	N	0.500694678	None	None	N
V/M	0.7812	likely_pathogenic	0.7491	pathogenic	-0.43	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/N	0.9945	likely_pathogenic	0.9939	pathogenic	-2.155	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/P	0.995	likely_pathogenic	0.9945	pathogenic	-0.842	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
V/Q	0.9946	likely_pathogenic	0.9941	pathogenic	-1.86	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/R	0.9938	likely_pathogenic	0.9935	pathogenic	-1.684	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/S	0.9703	likely_pathogenic	0.9659	pathogenic	-2.752	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/T	0.8886	likely_pathogenic	0.8778	pathogenic	-2.302	Highly Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
V/W	0.9988	likely_pathogenic	0.9987	pathogenic	-1.788	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/Y	0.9947	likely_pathogenic	0.9936	pathogenic	-1.356	Destabilizing	1.0	D	0.811	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.