TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29518	88777;88778;88779	chr2:178554907;178554906;178554905	chr2:179419634;179419633;179419632
N2AB	27877	83854;83855;83856	chr2:178554907;178554906;178554905	chr2:179419634;179419633;179419632
N2A	26950	81073;81074;81075	chr2:178554907;178554906;178554905	chr2:179419634;179419633;179419632
N2B	20453	61582;61583;61584	chr2:178554907;178554906;178554905	chr2:179419634;179419633;179419632
Novex-1	20578	61957;61958;61959	chr2:178554907;178554906;178554905	chr2:179419634;179419633;179419632
Novex-2	20645	62158;62159;62160	chr2:178554907;178554906;178554905	chr2:179419634;179419633;179419632
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-146
• Domain position: 75
• Structural Position: 162
• Q(SASA): 0.579
• 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
A/V	None	None	0.989	N	0.313	0.326	0.536287059136	gnomAD-4.0.0	3.60098E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.93752E-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	0.5467	ambiguous	0.5966	pathogenic	-0.719	Destabilizing	1.0	D	0.392	neutral	None	None	None	None	I
A/D	0.3648	ambiguous	0.3781	ambiguous	-0.575	Destabilizing	0.994	D	0.377	neutral	N	0.449422227	None	None	I
A/E	0.3446	ambiguous	0.3489	ambiguous	-0.729	Destabilizing	0.983	D	0.345	neutral	None	None	None	None	I
A/F	0.4667	ambiguous	0.4815	ambiguous	-0.88	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	I
A/G	0.1999	likely_benign	0.213	benign	-0.172	Destabilizing	0.948	D	0.312	neutral	N	0.449595586	None	None	I
A/H	0.5478	ambiguous	0.5747	pathogenic	-0.207	Destabilizing	1.0	D	0.49	neutral	None	None	None	None	I
A/I	0.2449	likely_benign	0.2512	benign	-0.325	Destabilizing	0.998	D	0.387	neutral	None	None	None	None	I
A/K	0.5511	ambiguous	0.5522	ambiguous	-0.545	Destabilizing	0.983	D	0.347	neutral	None	None	None	None	I
A/L	0.2279	likely_benign	0.241	benign	-0.325	Destabilizing	0.992	D	0.375	neutral	None	None	None	None	I
A/M	0.2735	likely_benign	0.2882	benign	-0.483	Destabilizing	1.0	D	0.395	neutral	None	None	None	None	I
A/N	0.2778	likely_benign	0.3134	benign	-0.183	Destabilizing	0.995	D	0.392	neutral	None	None	None	None	I
A/P	0.2036	likely_benign	0.2285	benign	-0.244	Destabilizing	0.997	D	0.387	neutral	N	0.427777519	None	None	I
A/Q	0.416	ambiguous	0.4316	ambiguous	-0.462	Destabilizing	0.998	D	0.376	neutral	None	None	None	None	I
A/R	0.5111	ambiguous	0.5068	ambiguous	-0.099	Destabilizing	0.998	D	0.384	neutral	None	None	None	None	I
A/S	0.1011	likely_benign	0.1102	benign	-0.342	Destabilizing	0.418	N	0.256	neutral	N	0.399355979	None	None	I
A/T	0.095	likely_benign	0.1015	benign	-0.427	Destabilizing	0.956	D	0.283	neutral	N	0.46046594	None	None	I
A/V	0.1252	likely_benign	0.1267	benign	-0.244	Destabilizing	0.989	D	0.313	neutral	N	0.446075278	None	None	I
A/W	0.8338	likely_pathogenic	0.8482	pathogenic	-1.004	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
A/Y	0.5869	likely_pathogenic	0.6207	pathogenic	-0.669	Destabilizing	0.999	D	0.483	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.