TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25217	75874;75875;75876	chr2:178570483;178570482;178570481	chr2:179435210;179435209;179435208
N2AB	23576	70951;70952;70953	chr2:178570483;178570482;178570481	chr2:179435210;179435209;179435208
N2A	22649	68170;68171;68172	chr2:178570483;178570482;178570481	chr2:179435210;179435209;179435208
N2B	16152	48679;48680;48681	chr2:178570483;178570482;178570481	chr2:179435210;179435209;179435208
Novex-1	16277	49054;49055;49056	chr2:178570483;178570482;178570481	chr2:179435210;179435209;179435208
Novex-2	16344	49255;49256;49257	chr2:178570483;178570482;178570481	chr2:179435210;179435209;179435208
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-71
• Domain position: 14
• Structural Position: 15
• Q(SASA): 0.4194
• 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	rs1292869028	-0.503	0.014	N	0.187	0.057	0.257786959452	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
V/I	rs1292869028	-0.503	0.014	N	0.187	0.057	0.257786959452	gnomAD-4.0.0	1.59231E-06	None	None	None	None	N	None	0	0	None	0	2.78396E-05	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	0.396	ambiguous	0.4044	ambiguous	-1.191	Destabilizing	0.822	D	0.443	neutral	N	0.473600965	None	None	N
V/C	0.7457	likely_pathogenic	0.7962	pathogenic	-1.079	Destabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
V/D	0.7998	likely_pathogenic	0.8116	pathogenic	-0.922	Destabilizing	0.99	D	0.803	deleterious	N	0.519622071	None	None	N
V/E	0.6447	likely_pathogenic	0.6566	pathogenic	-0.974	Destabilizing	0.993	D	0.76	deleterious	None	None	None	None	N
V/F	0.2595	likely_benign	0.2675	benign	-1.247	Destabilizing	0.942	D	0.741	deleterious	N	0.498012324	None	None	N
V/G	0.4428	ambiguous	0.4653	ambiguous	-1.421	Destabilizing	0.971	D	0.799	deleterious	N	0.509115139	None	None	N
V/H	0.8041	likely_pathogenic	0.8334	pathogenic	-1.005	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
V/I	0.0612	likely_benign	0.0627	benign	-0.687	Destabilizing	0.014	N	0.187	neutral	N	0.462665591	None	None	N
V/K	0.5389	ambiguous	0.5617	ambiguous	-0.833	Destabilizing	0.978	D	0.762	deleterious	None	None	None	None	N
V/L	0.2168	likely_benign	0.2326	benign	-0.687	Destabilizing	0.247	N	0.323	neutral	N	0.499954543	None	None	N
V/M	0.154	likely_benign	0.1549	benign	-0.549	Destabilizing	0.956	D	0.668	neutral	None	None	None	None	N
V/N	0.5729	likely_pathogenic	0.5956	pathogenic	-0.627	Destabilizing	0.993	D	0.802	deleterious	None	None	None	None	N
V/P	0.7514	likely_pathogenic	0.7909	pathogenic	-0.821	Destabilizing	0.993	D	0.777	deleterious	None	None	None	None	N
V/Q	0.5554	ambiguous	0.5803	pathogenic	-0.883	Destabilizing	0.993	D	0.771	deleterious	None	None	None	None	N
V/R	0.5312	ambiguous	0.5697	pathogenic	-0.359	Destabilizing	0.993	D	0.801	deleterious	None	None	None	None	N
V/S	0.4965	ambiguous	0.5214	ambiguous	-1.142	Destabilizing	0.978	D	0.761	deleterious	None	None	None	None	N
V/T	0.3451	ambiguous	0.3563	ambiguous	-1.089	Destabilizing	0.86	D	0.563	neutral	None	None	None	None	N
V/W	0.8896	likely_pathogenic	0.9089	pathogenic	-1.332	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
V/Y	0.6841	likely_pathogenic	0.7276	pathogenic	-1.008	Destabilizing	0.978	D	0.757	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.