TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9734	29425;29426;29427	chr2:178706674;178706673;178706672	chr2:179571401;179571400;179571399
N2AB	9417	28474;28475;28476	chr2:178706674;178706673;178706672	chr2:179571401;179571400;179571399
N2A	8490	25693;25694;25695	chr2:178706674;178706673;178706672	chr2:179571401;179571400;179571399
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: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-83
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.4227
• 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	None	None	1.0	None	0.591	0.452	0.416956310301	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9581	likely_pathogenic	0.8952	pathogenic	-0.525	Destabilizing	1.0	D	0.563	neutral	None	None	None	None	N
G/C	0.9928	likely_pathogenic	0.9795	pathogenic	-0.736	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	N
G/D	0.9845	likely_pathogenic	0.9628	pathogenic	-0.752	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
G/E	0.9923	likely_pathogenic	0.9722	pathogenic	-0.816	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
G/F	0.9967	likely_pathogenic	0.9911	pathogenic	-0.843	Destabilizing	1.0	D	0.56	neutral	None	None	None	None	N
G/H	0.9983	likely_pathogenic	0.9941	pathogenic	-1.162	Destabilizing	1.0	D	0.561	neutral	None	None	None	None	N
G/I	0.9961	likely_pathogenic	0.9891	pathogenic	-0.203	Destabilizing	1.0	D	0.57	neutral	None	None	None	None	N
G/K	0.9976	likely_pathogenic	0.9921	pathogenic	-1.113	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
G/L	0.9943	likely_pathogenic	0.9849	pathogenic	-0.203	Destabilizing	1.0	D	0.608	neutral	None	None	None	None	N
G/M	0.9968	likely_pathogenic	0.9898	pathogenic	-0.243	Destabilizing	1.0	D	0.578	neutral	None	None	None	None	N
G/N	0.9841	likely_pathogenic	0.9594	pathogenic	-0.735	Destabilizing	1.0	D	0.594	neutral	None	None	None	None	N
G/P	0.9994	likely_pathogenic	0.9984	pathogenic	-0.269	Destabilizing	1.0	D	0.596	neutral	None	None	None	None	N
G/Q	0.9959	likely_pathogenic	0.9848	pathogenic	-0.888	Destabilizing	1.0	D	0.587	neutral	None	None	None	None	N
G/R	0.9955	likely_pathogenic	0.9847	pathogenic	-0.844	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	N
G/S	0.9307	likely_pathogenic	0.815	pathogenic	-0.986	Destabilizing	1.0	D	0.6	neutral	None	None	None	None	N
G/T	0.9889	likely_pathogenic	0.9687	pathogenic	-0.968	Destabilizing	1.0	D	0.606	neutral	None	None	None	None	N
G/V	0.9916	likely_pathogenic	0.9762	pathogenic	-0.269	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	N
G/W	0.9931	likely_pathogenic	0.9764	pathogenic	-1.21	Destabilizing	1.0	D	0.581	neutral	None	None	None	None	N
G/Y	0.9946	likely_pathogenic	0.9854	pathogenic	-0.787	Destabilizing	1.0	D	0.555	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.