TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31563	94912;94913;94914	chr2:178546741;178546740;178546739	chr2:179411468;179411467;179411466
N2AB	29922	89989;89990;89991	chr2:178546741;178546740;178546739	chr2:179411468;179411467;179411466
N2A	28995	87208;87209;87210	chr2:178546741;178546740;178546739	chr2:179411468;179411467;179411466
N2B	22498	67717;67718;67719	chr2:178546741;178546740;178546739	chr2:179411468;179411467;179411466
Novex-1	22623	68092;68093;68094	chr2:178546741;178546740;178546739	chr2:179411468;179411467;179411466
Novex-2	22690	68293;68294;68295	chr2:178546741;178546740;178546739	chr2:179411468;179411467;179411466
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-118
• Domain position: 58
• Structural Position: 75
• Q(SASA): 0.4073
• 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
I/T	None	None	0.007	N	0.182	0.167	0.482209950775	gnomAD-4.0.0	1.59129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85847E-06	0	0
I/V	None	None	0.267	N	0.189	0.168	0.580770577012	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-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
I/A	0.3317	likely_benign	0.249	benign	-1.121	Destabilizing	0.525	D	0.384	neutral	None	None	None	None	I
I/C	0.8327	likely_pathogenic	0.7804	pathogenic	-0.864	Destabilizing	0.998	D	0.353	neutral	None	None	None	None	I
I/D	0.87	likely_pathogenic	0.7557	pathogenic	-0.336	Destabilizing	0.728	D	0.365	neutral	None	None	None	None	I
I/E	0.8457	likely_pathogenic	0.7499	pathogenic	-0.371	Destabilizing	0.842	D	0.359	neutral	None	None	None	None	I
I/F	0.367	ambiguous	0.279	benign	-0.79	Destabilizing	0.966	D	0.4	neutral	N	0.454046108	None	None	I
I/G	0.7582	likely_pathogenic	0.6548	pathogenic	-1.381	Destabilizing	0.842	D	0.353	neutral	None	None	None	None	I
I/H	0.7833	likely_pathogenic	0.6505	pathogenic	-0.6	Destabilizing	0.974	D	0.375	neutral	None	None	None	None	I
I/K	0.8099	likely_pathogenic	0.6999	pathogenic	-0.72	Destabilizing	0.842	D	0.369	neutral	None	None	None	None	I
I/L	0.1332	likely_benign	0.1213	benign	-0.521	Destabilizing	0.267	N	0.177	neutral	N	0.387341113	None	None	I
I/M	0.1149	likely_benign	0.0998	benign	-0.509	Destabilizing	0.989	D	0.402	neutral	N	0.435633706	None	None	I
I/N	0.3249	likely_benign	0.21	benign	-0.547	Destabilizing	0.051	N	0.383	neutral	N	0.304914518	None	None	I
I/P	0.6443	likely_pathogenic	0.5378	ambiguous	-0.687	Destabilizing	0.974	D	0.409	neutral	None	None	None	None	I
I/Q	0.7451	likely_pathogenic	0.6222	pathogenic	-0.722	Destabilizing	0.974	D	0.43	neutral	None	None	None	None	I
I/R	0.7367	likely_pathogenic	0.6187	pathogenic	-0.179	Destabilizing	0.974	D	0.409	neutral	None	None	None	None	I
I/S	0.3787	ambiguous	0.264	benign	-1.133	Destabilizing	0.454	N	0.308	neutral	N	0.394072298	None	None	I
I/T	0.2399	likely_benign	0.1617	benign	-1.05	Destabilizing	0.007	N	0.182	neutral	N	0.360959802	None	None	I
I/V	0.0725	likely_benign	0.0683	benign	-0.687	Destabilizing	0.267	N	0.189	neutral	N	0.40467608	None	None	I
I/W	0.9067	likely_pathogenic	0.8698	pathogenic	-0.813	Destabilizing	0.998	D	0.437	neutral	None	None	None	None	I
I/Y	0.723	likely_pathogenic	0.6236	pathogenic	-0.584	Destabilizing	0.991	D	0.405	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.