TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23432	70519;70520;70521	chr2:178575838;178575837;178575836	chr2:179440565;179440564;179440563
N2AB	21791	65596;65597;65598	chr2:178575838;178575837;178575836	chr2:179440565;179440564;179440563
N2A	20864	62815;62816;62817	chr2:178575838;178575837;178575836	chr2:179440565;179440564;179440563
N2B	14367	43324;43325;43326	chr2:178575838;178575837;178575836	chr2:179440565;179440564;179440563
Novex-1	14492	43699;43700;43701	chr2:178575838;178575837;178575836	chr2:179440565;179440564;179440563
Novex-2	14559	43900;43901;43902	chr2:178575838;178575837;178575836	chr2:179440565;179440564;179440563
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-129
• Domain position: 88
• Structural Position: 177
• Q(SASA): 0.8205
• 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
V/G	None	None	1.0	D	0.791	0.765	0.928886388543	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.9831	likely_pathogenic	0.9864	pathogenic	-1.986	Destabilizing	0.999	D	0.778	deleterious	N	0.51602549	None	None	I
V/C	0.9902	likely_pathogenic	0.99	pathogenic	-1.66	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
V/D	0.9994	likely_pathogenic	0.9995	pathogenic	-2.63	Highly Destabilizing	1.0	D	0.825	deleterious	D	0.528649243	None	None	I
V/E	0.9982	likely_pathogenic	0.9987	pathogenic	-2.572	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
V/F	0.9887	likely_pathogenic	0.9914	pathogenic	-1.5	Destabilizing	1.0	D	0.865	deleterious	D	0.527888774	None	None	I
V/G	0.9822	likely_pathogenic	0.9845	pathogenic	-2.36	Highly Destabilizing	1.0	D	0.791	deleterious	D	0.528649243	None	None	I
V/H	0.9996	likely_pathogenic	0.9997	pathogenic	-1.914	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
V/I	0.1847	likely_benign	0.2208	benign	-1.008	Destabilizing	0.997	D	0.746	deleterious	N	0.488585483	None	None	I
V/K	0.9986	likely_pathogenic	0.999	pathogenic	-1.721	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
V/L	0.9638	likely_pathogenic	0.975	pathogenic	-1.008	Destabilizing	0.997	D	0.781	deleterious	D	0.526621327	None	None	I
V/M	0.9731	likely_pathogenic	0.9776	pathogenic	-0.894	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
V/N	0.9961	likely_pathogenic	0.997	pathogenic	-1.739	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
V/P	0.9963	likely_pathogenic	0.9973	pathogenic	-1.304	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
V/Q	0.9985	likely_pathogenic	0.9988	pathogenic	-1.874	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
V/R	0.9975	likely_pathogenic	0.998	pathogenic	-1.21	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
V/S	0.9918	likely_pathogenic	0.9929	pathogenic	-2.242	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
V/T	0.9788	likely_pathogenic	0.9781	pathogenic	-2.076	Highly Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	I
V/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.807	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
V/Y	0.9986	likely_pathogenic	0.9989	pathogenic	-1.515	Destabilizing	1.0	D	0.87	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.