TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35632	107119;107120;107121	chr2:178528857;178528856;178528855	chr2:179393584;179393583;179393582
N2AB	33991	102196;102197;102198	chr2:178528857;178528856;178528855	chr2:179393584;179393583;179393582
N2A	33064	99415;99416;99417	chr2:178528857;178528856;178528855	chr2:179393584;179393583;179393582
N2B	26567	79924;79925;79926	chr2:178528857;178528856;178528855	chr2:179393584;179393583;179393582
Novex-1	26692	80299;80300;80301	chr2:178528857;178528856;178528855	chr2:179393584;179393583;179393582
Novex-2	26759	80500;80501;80502	chr2:178528857;178528856;178528855	chr2:179393584;179393583;179393582
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-167
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.5396
• 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/D	rs1210557316	None	0.006	N	0.247	0.437	0.253726318573	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
G/D	rs1210557316	None	0.006	N	0.247	0.437	0.253726318573	gnomAD-4.0.0	1.23928E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.47541E-07	1.09786E-05	0
G/V	rs1210557316	None	0.928	N	0.629	0.659	0.820686710369	gnomAD-4.0.0	6.84146E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99399E-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	0.2567	likely_benign	0.2721	benign	-0.204	Destabilizing	0.645	D	0.395	neutral	N	0.505343447	None	None	I
G/C	0.5806	likely_pathogenic	0.6007	pathogenic	-0.81	Destabilizing	0.993	D	0.638	neutral	N	0.506565004	None	None	I
G/D	0.2851	likely_benign	0.2927	benign	-0.524	Destabilizing	0.006	N	0.247	neutral	N	0.482626788	None	None	I
G/E	0.2888	likely_benign	0.3116	benign	-0.698	Destabilizing	0.031	N	0.289	neutral	None	None	None	None	I
G/F	0.8065	likely_pathogenic	0.8245	pathogenic	-1.026	Destabilizing	0.995	D	0.639	neutral	None	None	None	None	I
G/H	0.6694	likely_pathogenic	0.6815	pathogenic	-0.435	Destabilizing	0.995	D	0.525	neutral	None	None	None	None	I
G/I	0.6923	likely_pathogenic	0.714	pathogenic	-0.434	Destabilizing	0.945	D	0.636	neutral	None	None	None	None	I
G/K	0.6133	likely_pathogenic	0.6446	pathogenic	-0.643	Destabilizing	0.707	D	0.463	neutral	None	None	None	None	I
G/L	0.728	likely_pathogenic	0.7443	pathogenic	-0.434	Destabilizing	0.945	D	0.629	neutral	None	None	None	None	I
G/M	0.7628	likely_pathogenic	0.766	pathogenic	-0.473	Destabilizing	0.995	D	0.635	neutral	None	None	None	None	I
G/N	0.43	ambiguous	0.4221	ambiguous	-0.286	Destabilizing	0.809	D	0.463	neutral	None	None	None	None	I
G/P	0.9362	likely_pathogenic	0.9516	pathogenic	-0.328	Destabilizing	0.945	D	0.52	neutral	None	None	None	None	I
G/Q	0.5183	ambiguous	0.5397	ambiguous	-0.587	Destabilizing	0.894	D	0.511	neutral	None	None	None	None	I
G/R	0.4795	ambiguous	0.5282	ambiguous	-0.22	Destabilizing	0.864	D	0.52	neutral	N	0.506320692	None	None	I
G/S	0.1902	likely_benign	0.202	benign	-0.403	Destabilizing	0.477	N	0.436	neutral	N	0.505954226	None	None	I
G/T	0.3926	ambiguous	0.3947	ambiguous	-0.512	Destabilizing	0.894	D	0.473	neutral	None	None	None	None	I
G/V	0.5191	ambiguous	0.5465	ambiguous	-0.328	Destabilizing	0.928	D	0.629	neutral	N	0.506320692	None	None	I
G/W	0.6942	likely_pathogenic	0.7314	pathogenic	-1.156	Destabilizing	0.995	D	0.56	neutral	None	None	None	None	I
G/Y	0.7218	likely_pathogenic	0.7492	pathogenic	-0.809	Destabilizing	0.995	D	0.636	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.