TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22727	68404;68405;68406	chr2:178578851;178578850;178578849	chr2:179443578;179443577;179443576
N2AB	21086	63481;63482;63483	chr2:178578851;178578850;178578849	chr2:179443578;179443577;179443576
N2A	20159	60700;60701;60702	chr2:178578851;178578850;178578849	chr2:179443578;179443577;179443576
N2B	13662	41209;41210;41211	chr2:178578851;178578850;178578849	chr2:179443578;179443577;179443576
Novex-1	13787	41584;41585;41586	chr2:178578851;178578850;178578849	chr2:179443578;179443577;179443576
Novex-2	13854	41785;41786;41787	chr2:178578851;178578850;178578849	chr2:179443578;179443577;179443576
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-52
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.1655
• 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
G/V	rs2047052144	None	1.0	D	0.906	0.591	0.752597319067	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
G/V	rs2047052144	None	1.0	D	0.906	0.591	0.752597319067	gnomAD-4.0.0	6.57756E-06	None	None	None	None	N	None	0	6.55308E-05	None	0	0	None	0	0	0	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	0.4978	ambiguous	0.6111	pathogenic	-0.697	Destabilizing	1.0	D	0.707	prob.neutral	D	0.526585328	None	None	N
G/C	0.8184	likely_pathogenic	0.8876	pathogenic	-1.04	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
G/D	0.9666	likely_pathogenic	0.9833	pathogenic	-1.023	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
G/E	0.9729	likely_pathogenic	0.9854	pathogenic	-1.145	Destabilizing	1.0	D	0.916	deleterious	D	0.526331838	None	None	N
G/F	0.9923	likely_pathogenic	0.9955	pathogenic	-1.224	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
G/H	0.9817	likely_pathogenic	0.9911	pathogenic	-0.997	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
G/I	0.9858	likely_pathogenic	0.9909	pathogenic	-0.603	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
G/K	0.9907	likely_pathogenic	0.9956	pathogenic	-1.063	Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
G/L	0.9775	likely_pathogenic	0.9849	pathogenic	-0.603	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
G/M	0.9825	likely_pathogenic	0.9891	pathogenic	-0.526	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/N	0.9593	likely_pathogenic	0.9778	pathogenic	-0.726	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
G/P	0.9981	likely_pathogenic	0.9985	pathogenic	-0.598	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
G/Q	0.9744	likely_pathogenic	0.985	pathogenic	-1.035	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
G/R	0.9696	likely_pathogenic	0.9843	pathogenic	-0.641	Destabilizing	1.0	D	0.919	deleterious	N	0.519330399	None	None	N
G/S	0.2554	likely_benign	0.3118	benign	-0.942	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
G/T	0.7945	likely_pathogenic	0.8609	pathogenic	-0.999	Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
G/V	0.9626	likely_pathogenic	0.9772	pathogenic	-0.598	Destabilizing	1.0	D	0.906	deleterious	D	0.538448612	None	None	N
G/W	0.9722	likely_pathogenic	0.9854	pathogenic	-1.389	Destabilizing	1.0	D	0.86	deleterious	D	0.539209081	None	None	N
G/Y	0.9862	likely_pathogenic	0.9928	pathogenic	-1.039	Destabilizing	1.0	D	0.877	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.