TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35457	106594;106595;106596	chr2:178530246;178530245;178530244	chr2:179394973;179394972;179394971
N2AB	33816	101671;101672;101673	chr2:178530246;178530245;178530244	chr2:179394973;179394972;179394971
N2A	32889	98890;98891;98892	chr2:178530246;178530245;178530244	chr2:179394973;179394972;179394971
N2B	26392	79399;79400;79401	chr2:178530246;178530245;178530244	chr2:179394973;179394972;179394971
Novex-1	26517	79774;79775;79776	chr2:178530246;178530245;178530244	chr2:179394973;179394972;179394971
Novex-2	26584	79975;79976;79977	chr2:178530246;178530245;178530244	chr2:179394973;179394972;179394971
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-166
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.3814
• 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/V	None	None	1.0	D	0.678	0.583	0.719642243069	gnomAD-4.0.0	6.93753E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.06937E-07	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	0.3098	likely_benign	0.3133	benign	-0.224	Destabilizing	0.999	D	0.506	neutral	N	0.491964574	None	None	I
G/C	0.5236	ambiguous	0.4974	ambiguous	-0.853	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
G/D	0.2073	likely_benign	0.1907	benign	-0.717	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	I
G/E	0.2251	likely_benign	0.2098	benign	-0.893	Destabilizing	1.0	D	0.662	neutral	N	0.483353292	None	None	I
G/F	0.8254	likely_pathogenic	0.8228	pathogenic	-1.048	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
G/H	0.5357	ambiguous	0.5097	ambiguous	-0.395	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
G/I	0.6531	likely_pathogenic	0.6484	pathogenic	-0.468	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
G/K	0.4115	ambiguous	0.3864	ambiguous	-0.72	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	I
G/L	0.7262	likely_pathogenic	0.7296	pathogenic	-0.468	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
G/M	0.7359	likely_pathogenic	0.7356	pathogenic	-0.465	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	I
G/N	0.2797	likely_benign	0.2662	benign	-0.388	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
G/P	0.9742	likely_pathogenic	0.9773	pathogenic	-0.358	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
G/Q	0.3264	likely_benign	0.3102	benign	-0.707	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
G/R	0.2948	likely_benign	0.2693	benign	-0.237	Destabilizing	1.0	D	0.662	neutral	N	0.506194488	None	None	I
G/S	0.1293	likely_benign	0.1262	benign	-0.487	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
G/T	0.3878	ambiguous	0.3898	ambiguous	-0.603	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
G/V	0.5637	ambiguous	0.5648	pathogenic	-0.358	Destabilizing	1.0	D	0.678	prob.neutral	D	0.522439092	None	None	I
G/W	0.6556	likely_pathogenic	0.639	pathogenic	-1.168	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
G/Y	0.6879	likely_pathogenic	0.6713	pathogenic	-0.834	Destabilizing	1.0	D	0.687	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.