TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21327	64204;64205;64206	chr2:178587232;178587231;178587230	chr2:179451959;179451958;179451957
N2AB	19686	59281;59282;59283	chr2:178587232;178587231;178587230	chr2:179451959;179451958;179451957
N2A	18759	56500;56501;56502	chr2:178587232;178587231;178587230	chr2:179451959;179451958;179451957
N2B	12262	37009;37010;37011	chr2:178587232;178587231;178587230	chr2:179451959;179451958;179451957
Novex-1	12387	37384;37385;37386	chr2:178587232;178587231;178587230	chr2:179451959;179451958;179451957
Novex-2	12454	37585;37586;37587	chr2:178587232;178587231;178587230	chr2:179451959;179451958;179451957
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: Fn3-42
• Domain position: 62
• Structural Position: 93
• Q(SASA): 0.1188
• 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	rs779165086	-0.335	0.046	N	0.181	0.098	0.380564188046	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.9E-06	0
V/I	rs779165086	-0.335	0.046	N	0.181	0.098	0.380564188046	gnomAD-4.0.0	6.36973E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.73164E-05	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	0.5787	likely_pathogenic	0.5525	ambiguous	-2.06	Highly Destabilizing	0.939	D	0.63	neutral	N	0.520738034	None	None	N
V/C	0.8163	likely_pathogenic	0.8169	pathogenic	-1.592	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
V/D	0.9824	likely_pathogenic	0.9795	pathogenic	-2.747	Highly Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
V/E	0.9595	likely_pathogenic	0.9559	pathogenic	-2.509	Highly Destabilizing	0.997	D	0.824	deleterious	D	0.531426584	None	None	N
V/F	0.4292	ambiguous	0.4514	ambiguous	-1.28	Destabilizing	0.986	D	0.79	deleterious	None	None	None	None	N
V/G	0.8137	likely_pathogenic	0.7976	pathogenic	-2.622	Highly Destabilizing	0.997	D	0.84	deleterious	D	0.531426584	None	None	N
V/H	0.9738	likely_pathogenic	0.9743	pathogenic	-2.47	Highly Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
V/I	0.0673	likely_benign	0.0696	benign	-0.48	Destabilizing	0.046	N	0.181	neutral	N	0.443735901	None	None	N
V/K	0.9719	likely_pathogenic	0.9682	pathogenic	-1.827	Destabilizing	0.993	D	0.827	deleterious	None	None	None	None	N
V/L	0.2852	likely_benign	0.287	benign	-0.48	Destabilizing	0.76	D	0.565	neutral	N	0.499258323	None	None	N
V/M	0.2949	likely_benign	0.304	benign	-0.462	Destabilizing	0.986	D	0.719	prob.delet.	None	None	None	None	N
V/N	0.94	likely_pathogenic	0.9346	pathogenic	-2.183	Highly Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	N
V/P	0.9563	likely_pathogenic	0.948	pathogenic	-0.979	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	N
V/Q	0.9469	likely_pathogenic	0.943	pathogenic	-1.988	Destabilizing	0.998	D	0.859	deleterious	None	None	None	None	N
V/R	0.9598	likely_pathogenic	0.9529	pathogenic	-1.714	Destabilizing	0.998	D	0.874	deleterious	None	None	None	None	N
V/S	0.8367	likely_pathogenic	0.8205	pathogenic	-2.791	Highly Destabilizing	0.993	D	0.823	deleterious	None	None	None	None	N
V/T	0.7138	likely_pathogenic	0.7025	pathogenic	-2.397	Highly Destabilizing	0.953	D	0.675	prob.neutral	None	None	None	None	N
V/W	0.9742	likely_pathogenic	0.9756	pathogenic	-1.849	Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	N
V/Y	0.9046	likely_pathogenic	0.9057	pathogenic	-1.433	Destabilizing	0.998	D	0.786	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.