TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15784	47575;47576;47577	chr2:178618001;178618000;178617999	chr2:179482728;179482727;179482726
N2AB	14143	42652;42653;42654	chr2:178618001;178618000;178617999	chr2:179482728;179482727;179482726
N2A	13216	39871;39872;39873	chr2:178618001;178618000;178617999	chr2:179482728;179482727;179482726
N2B	6719	20380;20381;20382	chr2:178618001;178618000;178617999	chr2:179482728;179482727;179482726
Novex-1	6844	20755;20756;20757	chr2:178618001;178618000;178617999	chr2:179482728;179482727;179482726
Novex-2	6911	20956;20957;20958	chr2:178618001;178618000;178617999	chr2:179482728;179482727;179482726
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-2
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.6237
• 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
Y/F	None	None	0.006	N	0.201	0.189	0.323342291347	gnomAD-4.0.0	1.5937E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86272E-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
Y/A	0.5024	ambiguous	0.5529	ambiguous	-0.779	Destabilizing	0.329	N	0.365	neutral	None	None	None	None	I
Y/C	0.3154	likely_benign	0.3297	benign	0.085	Stabilizing	0.993	D	0.356	neutral	N	0.495648666	None	None	I
Y/D	0.2407	likely_benign	0.2724	benign	0.945	Stabilizing	0.006	N	0.239	neutral	N	0.393086301	None	None	I
Y/E	0.5237	ambiguous	0.5825	pathogenic	0.924	Stabilizing	0.543	D	0.425	neutral	None	None	None	None	I
Y/F	0.1148	likely_benign	0.1243	benign	-0.424	Destabilizing	0.006	N	0.201	neutral	N	0.44125287	None	None	I
Y/G	0.428	ambiguous	0.4451	ambiguous	-0.966	Destabilizing	0.495	N	0.413	neutral	None	None	None	None	I
Y/H	0.2448	likely_benign	0.2751	benign	0.136	Stabilizing	0.975	D	0.359	neutral	N	0.471863047	None	None	I
Y/I	0.5469	ambiguous	0.6298	pathogenic	-0.312	Destabilizing	0.704	D	0.427	neutral	None	None	None	None	I
Y/K	0.5275	ambiguous	0.6153	pathogenic	0.166	Stabilizing	0.704	D	0.466	neutral	None	None	None	None	I
Y/L	0.5648	likely_pathogenic	0.6143	pathogenic	-0.312	Destabilizing	0.329	N	0.367	neutral	None	None	None	None	I
Y/M	0.5641	likely_pathogenic	0.6224	pathogenic	-0.081	Destabilizing	0.981	D	0.353	neutral	None	None	None	None	I
Y/N	0.1271	likely_benign	0.1383	benign	-0.002	Destabilizing	0.473	N	0.457	neutral	N	0.463472577	None	None	I
Y/P	0.9596	likely_pathogenic	0.9669	pathogenic	-0.448	Destabilizing	0.944	D	0.413	neutral	None	None	None	None	I
Y/Q	0.4951	ambiguous	0.5598	ambiguous	0.021	Stabilizing	0.944	D	0.393	neutral	None	None	None	None	I
Y/R	0.4494	ambiguous	0.5378	ambiguous	0.463	Stabilizing	0.944	D	0.42	neutral	None	None	None	None	I
Y/S	0.212	likely_benign	0.2582	benign	-0.468	Destabilizing	0.029	N	0.169	neutral	N	0.460460241	None	None	I
Y/T	0.3526	ambiguous	0.4254	ambiguous	-0.4	Destabilizing	0.543	D	0.442	neutral	None	None	None	None	I
Y/V	0.4372	ambiguous	0.5092	ambiguous	-0.448	Destabilizing	0.704	D	0.448	neutral	None	None	None	None	I
Y/W	0.494	ambiguous	0.5159	ambiguous	-0.524	Destabilizing	0.007	N	0.227	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.