TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19376	58351;58352;58353	chr2:178594368;178594367;178594366	chr2:179459095;179459094;179459093
N2AB	17735	53428;53429;53430	chr2:178594368;178594367;178594366	chr2:179459095;179459094;179459093
N2A	16808	50647;50648;50649	chr2:178594368;178594367;178594366	chr2:179459095;179459094;179459093
N2B	10311	31156;31157;31158	chr2:178594368;178594367;178594366	chr2:179459095;179459094;179459093
Novex-1	10436	31531;31532;31533	chr2:178594368;178594367;178594366	chr2:179459095;179459094;179459093
Novex-2	10503	31732;31733;31734	chr2:178594368;178594367;178594366	chr2:179459095;179459094;179459093
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-28
• Domain position: 93
• Structural Position: 126
• Q(SASA): 0.284
• 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
P/S	None	None	0.995	N	0.818	0.362	0.306377322295	gnomAD-4.0.0	3.46185E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.71818E-06	0	3.35357E-05
P/T	rs1226665355	-1.231	0.997	N	0.789	0.389	0.371344866733	gnomAD-2.1.1	4.23E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.2E-06	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
P/A	0.1671	likely_benign	0.1829	benign	-0.889	Destabilizing	0.603	D	0.419	neutral	N	0.469889711	None	None	N
P/C	0.9446	likely_pathogenic	0.9403	pathogenic	-0.696	Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
P/D	0.9649	likely_pathogenic	0.9583	pathogenic	-0.627	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
P/E	0.8866	likely_pathogenic	0.8638	pathogenic	-0.712	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
P/F	0.9778	likely_pathogenic	0.9646	pathogenic	-0.9	Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
P/G	0.7913	likely_pathogenic	0.7782	pathogenic	-1.088	Destabilizing	0.993	D	0.845	deleterious	None	None	None	None	N
P/H	0.8955	likely_pathogenic	0.8595	pathogenic	-0.602	Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
P/I	0.8914	likely_pathogenic	0.8519	pathogenic	-0.493	Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
P/K	0.9488	likely_pathogenic	0.9308	pathogenic	-0.769	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
P/L	0.7262	likely_pathogenic	0.6611	pathogenic	-0.493	Destabilizing	0.997	D	0.815	deleterious	N	0.469284281	None	None	N
P/M	0.867	likely_pathogenic	0.8286	pathogenic	-0.406	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
P/N	0.9114	likely_pathogenic	0.8828	pathogenic	-0.487	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
P/Q	0.7804	likely_pathogenic	0.7369	pathogenic	-0.736	Destabilizing	1.0	D	0.841	deleterious	N	0.502899125	None	None	N
P/R	0.8925	likely_pathogenic	0.8604	pathogenic	-0.189	Destabilizing	0.999	D	0.881	deleterious	N	0.488010873	None	None	N
P/S	0.5864	likely_pathogenic	0.5584	ambiguous	-0.9	Destabilizing	0.995	D	0.818	deleterious	N	0.477451036	None	None	N
P/T	0.5639	ambiguous	0.5144	ambiguous	-0.883	Destabilizing	0.997	D	0.789	deleterious	N	0.479007971	None	None	N
P/V	0.7367	likely_pathogenic	0.6863	pathogenic	-0.589	Destabilizing	0.998	D	0.774	deleterious	None	None	None	None	N
P/W	0.9907	likely_pathogenic	0.9854	pathogenic	-0.991	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
P/Y	0.9677	likely_pathogenic	0.9508	pathogenic	-0.712	Destabilizing	1.0	D	0.93	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.