TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5860	17803;17804;17805	chr2:178731087;178731086;178731085	chr2:179595814;179595813;179595812
N2AB	5543	16852;16853;16854	chr2:178731087;178731086;178731085	chr2:179595814;179595813;179595812
N2A	4616	14071;14072;14073	chr2:178731087;178731086;178731085	chr2:179595814;179595813;179595812
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: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-42
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.3088
• 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/D	rs754157651	-0.507	0.898	N	0.557	0.392	0.242825505644	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	1.77E-05	0
G/D	rs754157651	-0.507	0.898	N	0.557	0.392	0.242825505644	gnomAD-4.0.0	4.78975E-06	None	None	None	None	N	None	0	0	None	0	2.51978E-05	None	0	0	5.3971E-06	0	0
G/V	None	None	1.0	D	0.721	0.513	0.789514686668	gnomAD-4.0.0	6.8425E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99517E-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	0.2914	likely_benign	0.3407	ambiguous	-0.304	Destabilizing	1.0	D	0.561	neutral	N	0.5041438	None	None	N
G/C	0.3633	ambiguous	0.4565	ambiguous	-0.898	Destabilizing	1.0	D	0.717	prob.delet.	D	0.523262013	None	None	N
G/D	0.1813	likely_benign	0.2079	benign	-0.568	Destabilizing	0.898	D	0.557	neutral	N	0.472464286	None	None	N
G/E	0.2433	likely_benign	0.296	benign	-0.721	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
G/F	0.7527	likely_pathogenic	0.8239	pathogenic	-0.991	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
G/H	0.3819	ambiguous	0.4373	ambiguous	-0.462	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
G/I	0.6245	likely_pathogenic	0.7132	pathogenic	-0.449	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
G/K	0.3571	ambiguous	0.4244	ambiguous	-0.817	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
G/L	0.6744	likely_pathogenic	0.74	pathogenic	-0.449	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
G/M	0.6732	likely_pathogenic	0.7367	pathogenic	-0.595	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
G/N	0.2292	likely_benign	0.248	benign	-0.478	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
G/P	0.9742	likely_pathogenic	0.9825	pathogenic	-0.369	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
G/Q	0.2833	likely_benign	0.3247	benign	-0.744	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
G/R	0.2438	likely_benign	0.3033	benign	-0.365	Destabilizing	1.0	D	0.718	prob.delet.	N	0.521994565	None	None	N
G/S	0.1187	likely_benign	0.1316	benign	-0.621	Destabilizing	1.0	D	0.653	neutral	N	0.484518608	None	None	N
G/T	0.3538	ambiguous	0.4098	ambiguous	-0.703	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
G/V	0.5331	ambiguous	0.6304	pathogenic	-0.369	Destabilizing	1.0	D	0.721	prob.delet.	D	0.523262013	None	None	N
G/W	0.6289	likely_pathogenic	0.7106	pathogenic	-1.139	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
G/Y	0.5739	likely_pathogenic	0.6823	pathogenic	-0.801	Destabilizing	1.0	D	0.723	prob.delet.	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.