TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24432	73519;73520;73521	chr2:178572838;178572837;178572836	chr2:179437565;179437564;179437563
N2AB	22791	68596;68597;68598	chr2:178572838;178572837;178572836	chr2:179437565;179437564;179437563
N2A	21864	65815;65816;65817	chr2:178572838;178572837;178572836	chr2:179437565;179437564;179437563
N2B	15367	46324;46325;46326	chr2:178572838;178572837;178572836	chr2:179437565;179437564;179437563
Novex-1	15492	46699;46700;46701	chr2:178572838;178572837;178572836	chr2:179437565;179437564;179437563
Novex-2	15559	46900;46901;46902	chr2:178572838;178572837;178572836	chr2:179437565;179437564;179437563
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-132
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.4947
• 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
A/T	None	None	0.805	N	0.452	0.267	0.258283824007	gnomAD-4.0.0	1.59206E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85966E-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
A/C	0.6435	likely_pathogenic	0.6989	pathogenic	-0.659	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	N
A/D	0.7026	likely_pathogenic	0.8266	pathogenic	-0.526	Destabilizing	0.967	D	0.587	neutral	N	0.492272468	None	None	N
A/E	0.6559	likely_pathogenic	0.7796	pathogenic	-0.682	Destabilizing	0.975	D	0.52	neutral	None	None	None	None	N
A/F	0.6265	likely_pathogenic	0.7372	pathogenic	-0.832	Destabilizing	0.975	D	0.615	neutral	None	None	None	None	N
A/G	0.1985	likely_benign	0.266	benign	-0.218	Destabilizing	0.892	D	0.439	neutral	N	0.510678543	None	None	N
A/H	0.7625	likely_pathogenic	0.8367	pathogenic	-0.28	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
A/I	0.3669	ambiguous	0.5041	ambiguous	-0.265	Destabilizing	0.95	D	0.513	neutral	None	None	None	None	N
A/K	0.8287	likely_pathogenic	0.892	pathogenic	-0.612	Destabilizing	0.975	D	0.517	neutral	None	None	None	None	N
A/L	0.2703	likely_benign	0.3646	ambiguous	-0.265	Destabilizing	0.845	D	0.432	neutral	None	None	None	None	N
A/M	0.2929	likely_benign	0.4052	ambiguous	-0.374	Destabilizing	0.997	D	0.575	neutral	None	None	None	None	N
A/N	0.4259	ambiguous	0.5592	ambiguous	-0.219	Destabilizing	0.975	D	0.579	neutral	None	None	None	None	N
A/P	0.302	likely_benign	0.3779	ambiguous	-0.204	Destabilizing	0.983	D	0.526	neutral	N	0.499362812	None	None	N
A/Q	0.6125	likely_pathogenic	0.7082	pathogenic	-0.505	Destabilizing	0.987	D	0.556	neutral	None	None	None	None	N
A/R	0.7869	likely_pathogenic	0.8332	pathogenic	-0.144	Destabilizing	0.987	D	0.543	neutral	None	None	None	None	N
A/S	0.1195	likely_benign	0.1435	benign	-0.39	Destabilizing	0.426	N	0.312	neutral	N	0.507368879	None	None	N
A/T	0.1285	likely_benign	0.1718	benign	-0.472	Destabilizing	0.805	D	0.452	neutral	N	0.497081406	None	None	N
A/V	0.1742	likely_benign	0.2411	benign	-0.204	Destabilizing	0.056	N	0.313	neutral	N	0.478381267	None	None	N
A/W	0.9031	likely_pathogenic	0.9346	pathogenic	-0.982	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
A/Y	0.7469	likely_pathogenic	0.8301	pathogenic	-0.632	Destabilizing	0.987	D	0.627	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.