TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7578	22957;22958;22959	chr2:178721931;178721930;178721929	chr2:179586658;179586657;179586656
N2AB	7261	22006;22007;22008	chr2:178721931;178721930;178721929	chr2:179586658;179586657;179586656
N2A	6334	19225;19226;19227	chr2:178721931;178721930;178721929	chr2:179586658;179586657;179586656
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-60
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.2251
• 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/R	rs775145999	-0.29	0.977	N	0.477	0.315	0.587992605178	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
G/R	rs775145999	-0.29	0.977	N	0.477	0.315	0.587992605178	gnomAD-4.0.0	1.77926E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.33899E-05	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	0.1415	likely_benign	0.1489	benign	-0.274	Destabilizing	0.961	D	0.435	neutral	N	0.433489983	None	None	N
G/C	0.3031	likely_benign	0.3292	benign	-0.841	Destabilizing	1.0	D	0.631	neutral	N	0.46943214	None	None	N
G/D	0.4175	ambiguous	0.3834	ambiguous	-0.215	Destabilizing	0.031	N	0.206	neutral	N	0.399993485	None	None	N
G/E	0.4079	ambiguous	0.3967	ambiguous	-0.363	Destabilizing	0.304	N	0.336	neutral	None	None	None	None	N
G/F	0.6528	likely_pathogenic	0.6674	pathogenic	-0.931	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	N
G/H	0.5402	ambiguous	0.5502	ambiguous	-0.605	Destabilizing	1.0	D	0.555	neutral	None	None	None	None	N
G/I	0.4039	ambiguous	0.4081	ambiguous	-0.319	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
G/K	0.7027	likely_pathogenic	0.7018	pathogenic	-0.711	Destabilizing	0.304	N	0.349	neutral	None	None	None	None	N
G/L	0.4077	ambiguous	0.4213	ambiguous	-0.319	Destabilizing	0.996	D	0.532	neutral	None	None	None	None	N
G/M	0.522	ambiguous	0.538	ambiguous	-0.35	Destabilizing	1.0	D	0.59	neutral	None	None	None	None	N
G/N	0.3072	likely_benign	0.2955	benign	-0.351	Destabilizing	0.97	D	0.495	neutral	None	None	None	None	N
G/P	0.9415	likely_pathogenic	0.9421	pathogenic	-0.268	Destabilizing	0.999	D	0.527	neutral	None	None	None	None	N
G/Q	0.4276	ambiguous	0.4317	ambiguous	-0.599	Destabilizing	0.991	D	0.493	neutral	None	None	None	None	N
G/R	0.5144	ambiguous	0.5271	ambiguous	-0.365	Destabilizing	0.977	D	0.477	neutral	N	0.401244278	None	None	N
G/S	0.0857	likely_benign	0.0857	benign	-0.582	Destabilizing	0.961	D	0.458	neutral	N	0.385370749	None	None	N
G/T	0.1712	likely_benign	0.1748	benign	-0.648	Destabilizing	0.996	D	0.484	neutral	None	None	None	None	N
G/V	0.249	likely_benign	0.2532	benign	-0.268	Destabilizing	0.994	D	0.53	neutral	N	0.395915816	None	None	N
G/W	0.5224	ambiguous	0.54	ambiguous	-1.11	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	N
G/Y	0.586	likely_pathogenic	0.5952	pathogenic	-0.732	Destabilizing	0.999	D	0.591	neutral	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.