TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30556	91891;91892;91893	chr2:178550172;178550171;178550170	chr2:179414899;179414898;179414897
N2AB	28915	86968;86969;86970	chr2:178550172;178550171;178550170	chr2:179414899;179414898;179414897
N2A	27988	84187;84188;84189	chr2:178550172;178550171;178550170	chr2:179414899;179414898;179414897
N2B	21491	64696;64697;64698	chr2:178550172;178550171;178550170	chr2:179414899;179414898;179414897
Novex-1	21616	65071;65072;65073	chr2:178550172;178550171;178550170	chr2:179414899;179414898;179414897
Novex-2	21683	65272;65273;65274	chr2:178550172;178550171;178550170	chr2:179414899;179414898;179414897
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-149
• Domain position: 25
• Structural Position: 44
• Q(SASA): 0.2247
• Predicted PPI site: I

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/L	None	None	1.0	D	0.757	0.768	0.877019509546	gnomAD-4.0.0	1.36842E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79897E-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
P/A	0.7755	likely_pathogenic	0.751	pathogenic	-1.255	Destabilizing	1.0	D	0.787	deleterious	D	0.532916701	None	None	I
P/C	0.9771	likely_pathogenic	0.9736	pathogenic	-0.834	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
P/D	0.9992	likely_pathogenic	0.9991	pathogenic	-1.051	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
P/E	0.9972	likely_pathogenic	0.9966	pathogenic	-1.111	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
P/F	0.9984	likely_pathogenic	0.9983	pathogenic	-1.183	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
P/G	0.9817	likely_pathogenic	0.9776	pathogenic	-1.501	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
P/H	0.9957	likely_pathogenic	0.9949	pathogenic	-1.14	Destabilizing	1.0	D	0.711	prob.delet.	D	0.568671139	None	None	I
P/I	0.9752	likely_pathogenic	0.9756	pathogenic	-0.709	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
P/K	0.9983	likely_pathogenic	0.9978	pathogenic	-1.071	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
P/L	0.9354	likely_pathogenic	0.9296	pathogenic	-0.709	Destabilizing	1.0	D	0.757	deleterious	D	0.552080459	None	None	I
P/M	0.9884	likely_pathogenic	0.9876	pathogenic	-0.491	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
P/N	0.998	likely_pathogenic	0.9976	pathogenic	-0.761	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
P/Q	0.9918	likely_pathogenic	0.9897	pathogenic	-1.0	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
P/R	0.9935	likely_pathogenic	0.9921	pathogenic	-0.526	Destabilizing	1.0	D	0.78	deleterious	D	0.579520465	None	None	I
P/S	0.9684	likely_pathogenic	0.9621	pathogenic	-1.198	Destabilizing	1.0	D	0.8	deleterious	D	0.55251544	None	None	I
P/T	0.9639	likely_pathogenic	0.9581	pathogenic	-1.159	Destabilizing	1.0	D	0.791	deleterious	D	0.579013486	None	None	I
P/V	0.9428	likely_pathogenic	0.9432	pathogenic	-0.855	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
P/W	0.9993	likely_pathogenic	0.9993	pathogenic	-1.311	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
P/Y	0.9987	likely_pathogenic	0.9985	pathogenic	-1.035	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I

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.