TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18567	55924;55925;55926	chr2:178601298;178601297;178601296	chr2:179466025;179466024;179466023
N2AB	16926	51001;51002;51003	chr2:178601298;178601297;178601296	chr2:179466025;179466024;179466023
N2A	15999	48220;48221;48222	chr2:178601298;178601297;178601296	chr2:179466025;179466024;179466023
N2B	9502	28729;28730;28731	chr2:178601298;178601297;178601296	chr2:179466025;179466024;179466023
Novex-1	9627	29104;29105;29106	chr2:178601298;178601297;178601296	chr2:179466025;179466024;179466023
Novex-2	9694	29305;29306;29307	chr2:178601298;178601297;178601296	chr2:179466025;179466024;179466023
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-22
• Domain position: 89
• Structural Position: 123
• Q(SASA): 0.2041
• 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
T/S	rs773703444	-0.805	0.997	N	0.675	0.162	0.208816687407	gnomAD-2.1.1	4.3E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.36E-06	0
T/S	rs773703444	-0.805	0.997	N	0.675	0.162	0.208816687407	gnomAD-4.0.0	1.65949E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.96665E-06	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
T/A	0.6577	likely_pathogenic	0.5865	pathogenic	-0.791	Destabilizing	0.997	D	0.678	prob.neutral	N	0.496639305	None	None	N
T/C	0.9056	likely_pathogenic	0.9087	pathogenic	-0.246	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
T/D	0.9636	likely_pathogenic	0.9476	pathogenic	0.268	Stabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
T/E	0.971	likely_pathogenic	0.9542	pathogenic	0.402	Stabilizing	0.999	D	0.87	deleterious	None	None	None	None	N
T/F	0.9586	likely_pathogenic	0.9404	pathogenic	-0.574	Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
T/G	0.822	likely_pathogenic	0.7882	pathogenic	-1.146	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
T/H	0.9654	likely_pathogenic	0.9532	pathogenic	-1.119	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
T/I	0.8415	likely_pathogenic	0.8155	pathogenic	0.11	Stabilizing	0.999	D	0.889	deleterious	N	0.507162943	None	None	N
T/K	0.9753	likely_pathogenic	0.9554	pathogenic	0.135	Stabilizing	0.999	D	0.874	deleterious	None	None	None	None	N
T/L	0.5082	ambiguous	0.4765	ambiguous	0.11	Stabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
T/M	0.4036	ambiguous	0.3501	ambiguous	-0.024	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
T/N	0.7292	likely_pathogenic	0.6968	pathogenic	-0.179	Destabilizing	0.999	D	0.818	deleterious	N	0.47464356	None	None	N
T/P	0.9196	likely_pathogenic	0.8869	pathogenic	-0.158	Destabilizing	0.999	D	0.863	deleterious	N	0.451808306	None	None	N
T/Q	0.9606	likely_pathogenic	0.9414	pathogenic	-0.074	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
T/R	0.9784	likely_pathogenic	0.9594	pathogenic	-0.012	Destabilizing	0.999	D	0.869	deleterious	None	None	None	None	N
T/S	0.5719	likely_pathogenic	0.5423	ambiguous	-0.603	Destabilizing	0.997	D	0.675	prob.neutral	N	0.499428894	None	None	N
T/V	0.6955	likely_pathogenic	0.6705	pathogenic	-0.158	Destabilizing	0.998	D	0.736	deleterious	None	None	None	None	N
T/W	0.9928	likely_pathogenic	0.9885	pathogenic	-0.564	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
T/Y	0.9741	likely_pathogenic	0.9634	pathogenic	-0.214	Destabilizing	1.0	D	0.907	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.