TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8397	25414;25415;25416	chr2:178717685;178717684;178717683	chr2:179582412;179582411;179582410
N2AB	8080	24463;24464;24465	chr2:178717685;178717684;178717683	chr2:179582412;179582411;179582410
N2A	7153	21682;21683;21684	chr2:178717685;178717684;178717683	chr2:179582412;179582411;179582410
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-69
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.2869
• 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
G/V	rs1371524855	None	0.985	D	0.453	0.387	0.674180029473	gnomAD-4.0.0	4.77629E-06	None	None	None	None	N	None	0	0	None	0	5.55155E-05	None	0	0	0	1.43373E-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
G/A	0.3281	likely_benign	0.389	ambiguous	-0.396	Destabilizing	0.25	N	0.318	neutral	N	0.487203363	None	None	N
G/C	0.6206	likely_pathogenic	0.6849	pathogenic	-0.872	Destabilizing	0.997	D	0.464	neutral	None	None	None	None	N
G/D	0.2466	likely_benign	0.3374	benign	-0.667	Destabilizing	0.014	N	0.246	neutral	None	None	None	None	N
G/E	0.3696	ambiguous	0.4762	ambiguous	-0.815	Destabilizing	0.822	D	0.343	neutral	N	0.475149041	None	None	N
G/F	0.8888	likely_pathogenic	0.9291	pathogenic	-1.025	Destabilizing	0.996	D	0.437	neutral	None	None	None	None	N
G/H	0.5473	ambiguous	0.6397	pathogenic	-0.61	Destabilizing	0.989	D	0.371	neutral	None	None	None	None	N
G/I	0.8033	likely_pathogenic	0.8829	pathogenic	-0.465	Destabilizing	0.989	D	0.448	neutral	None	None	None	None	N
G/K	0.5751	likely_pathogenic	0.666	pathogenic	-0.956	Destabilizing	0.037	N	0.267	neutral	None	None	None	None	N
G/L	0.8212	likely_pathogenic	0.8705	pathogenic	-0.465	Destabilizing	0.924	D	0.463	neutral	None	None	None	None	N
G/M	0.7962	likely_pathogenic	0.8469	pathogenic	-0.523	Destabilizing	0.999	D	0.435	neutral	None	None	None	None	N
G/N	0.281	likely_benign	0.3145	benign	-0.598	Destabilizing	0.141	N	0.237	neutral	None	None	None	None	N
G/P	0.9881	likely_pathogenic	0.9945	pathogenic	-0.408	Destabilizing	0.97	D	0.379	neutral	None	None	None	None	N
G/Q	0.4504	ambiguous	0.5306	ambiguous	-0.869	Destabilizing	0.525	D	0.282	neutral	None	None	None	None	N
G/R	0.4113	ambiguous	0.5113	ambiguous	-0.474	Destabilizing	0.822	D	0.404	neutral	N	0.482670686	None	None	N
G/S	0.1351	likely_benign	0.1573	benign	-0.75	Destabilizing	0.077	N	0.131	neutral	None	None	None	None	N
G/T	0.4353	ambiguous	0.5207	ambiguous	-0.826	Destabilizing	0.86	D	0.349	neutral	None	None	None	None	N
G/V	0.6949	likely_pathogenic	0.8059	pathogenic	-0.408	Destabilizing	0.985	D	0.453	neutral	D	0.526071672	None	None	N
G/W	0.7643	likely_pathogenic	0.8475	pathogenic	-1.198	Destabilizing	0.999	D	0.489	neutral	D	0.526071672	None	None	N
G/Y	0.766	likely_pathogenic	0.8396	pathogenic	-0.854	Destabilizing	0.996	D	0.437	neutral	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.