TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8185	24778;24779;24780	chr2:178718553;178718552;178718551	chr2:179583280;179583279;179583278
N2AB	7868	23827;23828;23829	chr2:178718553;178718552;178718551	chr2:179583280;179583279;179583278
N2A	6941	21046;21047;21048	chr2:178718553;178718552;178718551	chr2:179583280;179583279;179583278
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-67
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.3812
• 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/E	rs1199728726	None	0.248	D	0.491	0.504	0.726976991548	gnomAD-4.0.0	1.02647E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.2594E-05	0	1.65706E-05
G/R	None	None	0.151	D	0.498	0.493	0.79385056502	gnomAD-4.0.0	1.59183E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88352E-05	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	0.2576	likely_benign	0.2656	benign	-0.333	Destabilizing	0.91	D	0.413	neutral	D	0.631487401	None	None	I
G/C	0.4637	ambiguous	0.4899	ambiguous	-0.926	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
G/D	0.2811	likely_benign	0.279	benign	-0.577	Destabilizing	0.942	D	0.574	neutral	None	None	None	None	I
G/E	0.3221	likely_benign	0.3077	benign	-0.741	Destabilizing	0.248	N	0.491	neutral	D	0.61405541	None	None	I
G/F	0.7799	likely_pathogenic	0.7806	pathogenic	-1.08	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	I
G/H	0.4469	ambiguous	0.4643	ambiguous	-0.537	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
G/I	0.6677	likely_pathogenic	0.6866	pathogenic	-0.496	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	I
G/K	0.4001	ambiguous	0.3905	ambiguous	-0.701	Destabilizing	0.304	N	0.445	neutral	None	None	None	None	I
G/L	0.6937	likely_pathogenic	0.6986	pathogenic	-0.496	Destabilizing	0.996	D	0.678	prob.neutral	None	None	None	None	I
G/M	0.7183	likely_pathogenic	0.729	pathogenic	-0.433	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
G/N	0.3046	likely_benign	0.3152	benign	-0.434	Destabilizing	0.985	D	0.487	neutral	None	None	None	None	I
G/P	0.9593	likely_pathogenic	0.9591	pathogenic	-0.41	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	I
G/Q	0.3667	ambiguous	0.3655	ambiguous	-0.749	Destabilizing	0.991	D	0.623	neutral	None	None	None	None	I
G/R	0.2913	likely_benign	0.2778	benign	-0.271	Destabilizing	0.151	N	0.498	neutral	D	0.622170454	None	None	I
G/S	0.1455	likely_benign	0.1485	benign	-0.588	Destabilizing	0.97	D	0.409	neutral	None	None	None	None	I
G/T	0.339	likely_benign	0.3615	ambiguous	-0.686	Destabilizing	0.996	D	0.634	neutral	None	None	None	None	I
G/V	0.5324	ambiguous	0.5512	ambiguous	-0.41	Destabilizing	0.994	D	0.659	neutral	D	0.64791037	None	None	I
G/W	0.6589	likely_pathogenic	0.6637	pathogenic	-1.198	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	I
G/Y	0.6503	likely_pathogenic	0.6543	pathogenic	-0.849	Destabilizing	0.999	D	0.698	prob.neutral	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.