TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35509	106750;106751;106752	chr2:178529966;178529965;178529964	chr2:179394693;179394692;179394691
N2AB	33868	101827;101828;101829	chr2:178529966;178529965;178529964	chr2:179394693;179394692;179394691
N2A	32941	99046;99047;99048	chr2:178529966;178529965;178529964	chr2:179394693;179394692;179394691
N2B	26444	79555;79556;79557	chr2:178529966;178529965;178529964	chr2:179394693;179394692;179394691
Novex-1	26569	79930;79931;79932	chr2:178529966;178529965;178529964	chr2:179394693;179394692;179394691
Novex-2	26636	80131;80132;80133	chr2:178529966;178529965;178529964	chr2:179394693;179394692;179394691
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-166
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.1159
• 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
I/T	rs1447572736	-1.983	0.322	N	0.547	0.574	0.70956276702	gnomAD-2.1.1	4.43E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.36E-06	0
I/T	rs1447572736	-1.983	0.322	N	0.547	0.574	0.70956276702	gnomAD-4.0.0	7.65311E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.94406E-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
I/A	0.5959	likely_pathogenic	0.6126	pathogenic	-1.565	Destabilizing	0.115	N	0.55	neutral	None	None	None	None	N
I/C	0.897	likely_pathogenic	0.9011	pathogenic	-1.653	Destabilizing	0.981	D	0.619	neutral	None	None	None	None	N
I/D	0.9577	likely_pathogenic	0.9602	pathogenic	-1.837	Destabilizing	0.932	D	0.667	neutral	None	None	None	None	N
I/E	0.8843	likely_pathogenic	0.8905	pathogenic	-1.838	Destabilizing	0.817	D	0.647	neutral	None	None	None	None	N
I/F	0.3619	ambiguous	0.4006	ambiguous	-1.448	Destabilizing	0.525	D	0.475	neutral	None	None	None	None	N
I/G	0.8639	likely_pathogenic	0.8744	pathogenic	-1.827	Destabilizing	0.817	D	0.642	neutral	None	None	None	None	N
I/H	0.9051	likely_pathogenic	0.9222	pathogenic	-1.086	Destabilizing	0.981	D	0.656	neutral	None	None	None	None	N
I/K	0.8017	likely_pathogenic	0.8354	pathogenic	-1.058	Destabilizing	0.771	D	0.631	neutral	D	0.52671173	None	None	N
I/L	0.1807	likely_benign	0.1932	benign	-0.914	Destabilizing	0.001	N	0.344	neutral	D	0.537508146	None	None	N
I/M	0.1782	likely_benign	0.194	benign	-0.935	Destabilizing	0.624	D	0.525	neutral	N	0.514848445	None	None	N
I/N	0.7026	likely_pathogenic	0.7155	pathogenic	-1.069	Destabilizing	0.932	D	0.667	neutral	None	None	None	None	N
I/P	0.9365	likely_pathogenic	0.9281	pathogenic	-1.104	Destabilizing	0.932	D	0.669	neutral	None	None	None	None	N
I/Q	0.8216	likely_pathogenic	0.8466	pathogenic	-1.344	Destabilizing	0.932	D	0.665	neutral	None	None	None	None	N
I/R	0.7381	likely_pathogenic	0.78	pathogenic	-0.522	Destabilizing	0.771	D	0.662	neutral	D	0.52671173	None	None	N
I/S	0.6526	likely_pathogenic	0.6747	pathogenic	-1.62	Destabilizing	0.688	D	0.607	neutral	None	None	None	None	N
I/T	0.5799	likely_pathogenic	0.6027	pathogenic	-1.513	Destabilizing	0.322	N	0.547	neutral	N	0.508100496	None	None	N
I/V	0.0828	likely_benign	0.0811	benign	-1.104	Destabilizing	0.001	N	0.348	neutral	N	0.393517724	None	None	N
I/W	0.9289	likely_pathogenic	0.945	pathogenic	-1.491	Destabilizing	0.981	D	0.662	neutral	None	None	None	None	N
I/Y	0.7973	likely_pathogenic	0.8306	pathogenic	-1.173	Destabilizing	0.817	D	0.608	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.