TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33180	99763;99764;99765	chr2:178537669;178537668;178537667	chr2:179402396;179402395;179402394
N2AB	31539	94840;94841;94842	chr2:178537669;178537668;178537667	chr2:179402396;179402395;179402394
N2A	30612	92059;92060;92061	chr2:178537669;178537668;178537667	chr2:179402396;179402395;179402394
N2B	24115	72568;72569;72570	chr2:178537669;178537668;178537667	chr2:179402396;179402395;179402394
Novex-1	24240	72943;72944;72945	chr2:178537669;178537668;178537667	chr2:179402396;179402395;179402394
Novex-2	24307	73144;73145;73146	chr2:178537669;178537668;178537667	chr2:179402396;179402395;179402394
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-156
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.1681
• 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
G/R	None	None	1.0	D	0.87	0.773	0.777805402551	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
G/A	0.8132	likely_pathogenic	0.8709	pathogenic	-0.447	Destabilizing	0.999	D	0.763	deleterious	D	0.5892281	None	None	I
G/C	0.9648	likely_pathogenic	0.9786	pathogenic	-0.94	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/D	0.9535	likely_pathogenic	0.9728	pathogenic	-1.019	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
G/E	0.9758	likely_pathogenic	0.9879	pathogenic	-1.19	Destabilizing	1.0	D	0.844	deleterious	D	0.539753556	None	None	I
G/F	0.9967	likely_pathogenic	0.9982	pathogenic	-1.176	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/H	0.9945	likely_pathogenic	0.9971	pathogenic	-0.685	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
G/I	0.9956	likely_pathogenic	0.9978	pathogenic	-0.597	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/K	0.9902	likely_pathogenic	0.9956	pathogenic	-1.078	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
G/L	0.9922	likely_pathogenic	0.9954	pathogenic	-0.597	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
G/M	0.9949	likely_pathogenic	0.9972	pathogenic	-0.546	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/N	0.9745	likely_pathogenic	0.9868	pathogenic	-0.697	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/P	0.9992	likely_pathogenic	0.9995	pathogenic	-0.514	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
G/Q	0.9831	likely_pathogenic	0.9914	pathogenic	-1.037	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
G/R	0.9757	likely_pathogenic	0.9883	pathogenic	-0.525	Destabilizing	1.0	D	0.87	deleterious	D	0.621700791	None	None	I
G/S	0.7532	likely_pathogenic	0.8557	pathogenic	-0.779	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
G/T	0.9631	likely_pathogenic	0.9784	pathogenic	-0.896	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/V	0.9882	likely_pathogenic	0.9941	pathogenic	-0.514	Destabilizing	1.0	D	0.841	deleterious	D	0.647844315	None	None	I
G/W	0.9926	likely_pathogenic	0.9956	pathogenic	-1.312	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/Y	0.9945	likely_pathogenic	0.997	pathogenic	-0.995	Destabilizing	1.0	D	0.839	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.