TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30905	92938;92939;92940	chr2:178548913;178548912;178548911	chr2:179413640;179413639;179413638
N2AB	29264	88015;88016;88017	chr2:178548913;178548912;178548911	chr2:179413640;179413639;179413638
N2A	28337	85234;85235;85236	chr2:178548913;178548912;178548911	chr2:179413640;179413639;179413638
N2B	21840	65743;65744;65745	chr2:178548913;178548912;178548911	chr2:179413640;179413639;179413638
Novex-1	21965	66118;66119;66120	chr2:178548913;178548912;178548911	chr2:179413640;179413639;179413638
Novex-2	22032	66319;66320;66321	chr2:178548913;178548912;178548911	chr2:179413640;179413639;179413638
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: Fn3-113
• Domain position: 85
• Structural Position: 118
• Q(SASA): 0.168
• 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	rs1698268798	None	1.0	D	0.939	0.683	0.772147790219	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/V	rs1698268798	None	1.0	D	0.939	0.683	0.772147790219	gnomAD-4.0.0	2.56197E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78549E-06	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	0.4991	ambiguous	0.4976	ambiguous	-0.742	Destabilizing	1.0	D	0.718	prob.delet.	D	0.539071636	None	None	N
G/C	0.8645	likely_pathogenic	0.8761	pathogenic	-1.113	Destabilizing	1.0	D	0.891	deleterious	D	0.539578615	None	None	N
G/D	0.9507	likely_pathogenic	0.9526	pathogenic	-1.208	Destabilizing	1.0	D	0.916	deleterious	D	0.538564657	None	None	N
G/E	0.9648	likely_pathogenic	0.967	pathogenic	-1.314	Destabilizing	1.0	D	0.945	deleterious	None	None	None	None	N
G/F	0.994	likely_pathogenic	0.9942	pathogenic	-1.253	Destabilizing	1.0	D	0.919	deleterious	None	None	None	None	N
G/H	0.9849	likely_pathogenic	0.9857	pathogenic	-1.041	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
G/I	0.9852	likely_pathogenic	0.9848	pathogenic	-0.59	Destabilizing	1.0	D	0.929	deleterious	None	None	None	None	N
G/K	0.9913	likely_pathogenic	0.9912	pathogenic	-1.079	Destabilizing	1.0	D	0.945	deleterious	None	None	None	None	N
G/L	0.9809	likely_pathogenic	0.9813	pathogenic	-0.59	Destabilizing	1.0	D	0.933	deleterious	None	None	None	None	N
G/M	0.9813	likely_pathogenic	0.9821	pathogenic	-0.513	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
G/N	0.9471	likely_pathogenic	0.95	pathogenic	-0.782	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
G/P	0.9979	likely_pathogenic	0.9981	pathogenic	-0.604	Destabilizing	1.0	D	0.941	deleterious	None	None	None	None	N
G/Q	0.9791	likely_pathogenic	0.9797	pathogenic	-1.087	Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
G/R	0.9792	likely_pathogenic	0.9795	pathogenic	-0.67	Destabilizing	1.0	D	0.947	deleterious	D	0.539071636	None	None	N
G/S	0.2266	likely_benign	0.2361	benign	-1.012	Destabilizing	1.0	D	0.835	deleterious	N	0.431368744	None	None	N
G/T	0.7876	likely_pathogenic	0.7913	pathogenic	-1.052	Destabilizing	1.0	D	0.936	deleterious	None	None	None	None	N
G/V	0.9595	likely_pathogenic	0.9596	pathogenic	-0.604	Destabilizing	1.0	D	0.939	deleterious	D	0.528475799	None	None	N
G/W	0.9827	likely_pathogenic	0.9847	pathogenic	-1.435	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
G/Y	0.9862	likely_pathogenic	0.9871	pathogenic	-1.073	Destabilizing	1.0	D	0.91	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.