TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18615	56068;56069;56070	chr2:178601061;178601060;178601059	chr2:179465788;179465787;179465786
N2AB	16974	51145;51146;51147	chr2:178601061;178601060;178601059	chr2:179465788;179465787;179465786
N2A	16047	48364;48365;48366	chr2:178601061;178601060;178601059	chr2:179465788;179465787;179465786
N2B	9550	28873;28874;28875	chr2:178601061;178601060;178601059	chr2:179465788;179465787;179465786
Novex-1	9675	29248;29249;29250	chr2:178601061;178601060;178601059	chr2:179465788;179465787;179465786
Novex-2	9742	29449;29450;29451	chr2:178601061;178601060;178601059	chr2:179465788;179465787;179465786
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: Fn3-23
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1694
• 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
I/S	rs1474944420	-3.104	0.018	N	0.598	0.197	0.642681104822	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
I/S	rs1474944420	-3.104	0.018	N	0.598	0.197	0.642681104822	gnomAD-4.0.0	3.42349E-06	None	None	None	None	N	None	0	8.95857E-05	None	0	0	None	0	0	0	0	1.65761E-05

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	0.4426	ambiguous	0.4432	ambiguous	-2.636	Highly Destabilizing	0.116	N	0.623	neutral	None	None	None	None	N
I/C	0.742	likely_pathogenic	0.7755	pathogenic	-1.776	Destabilizing	0.981	D	0.665	neutral	None	None	None	None	N
I/D	0.779	likely_pathogenic	0.8171	pathogenic	-3.295	Highly Destabilizing	0.527	D	0.668	neutral	None	None	None	None	N
I/E	0.6956	likely_pathogenic	0.7417	pathogenic	-3.15	Highly Destabilizing	0.69	D	0.666	neutral	None	None	None	None	N
I/F	0.2465	likely_benign	0.263	benign	-1.692	Destabilizing	0.457	N	0.68	prob.neutral	N	0.50578165	None	None	N
I/G	0.836	likely_pathogenic	0.8489	pathogenic	-3.074	Highly Destabilizing	0.241	N	0.624	neutral	None	None	None	None	N
I/H	0.4769	ambiguous	0.5118	ambiguous	-2.583	Highly Destabilizing	0.944	D	0.693	prob.neutral	None	None	None	None	N
I/K	0.5547	ambiguous	0.5793	pathogenic	-2.247	Highly Destabilizing	0.388	N	0.671	neutral	None	None	None	None	N
I/L	0.1625	likely_benign	0.1705	benign	-1.385	Destabilizing	0.001	N	0.372	neutral	N	0.490908198	None	None	N
I/M	0.1371	likely_benign	0.1425	benign	-1.117	Destabilizing	0.627	D	0.699	prob.neutral	N	0.474002131	None	None	N
I/N	0.2298	likely_benign	0.2483	benign	-2.405	Highly Destabilizing	0.001	N	0.637	neutral	N	0.496756735	None	None	N
I/P	0.9856	likely_pathogenic	0.9888	pathogenic	-1.785	Destabilizing	0.818	D	0.688	prob.neutral	None	None	None	None	N
I/Q	0.5348	ambiguous	0.5703	pathogenic	-2.401	Highly Destabilizing	0.818	D	0.692	prob.neutral	None	None	None	None	N
I/R	0.4233	ambiguous	0.4573	ambiguous	-1.7	Destabilizing	0.69	D	0.685	prob.neutral	None	None	None	None	N
I/S	0.3094	likely_benign	0.3406	ambiguous	-2.93	Highly Destabilizing	0.018	N	0.598	neutral	N	0.492657637	None	None	N
I/T	0.223	likely_benign	0.2254	benign	-2.682	Highly Destabilizing	0.193	N	0.643	neutral	N	0.497564812	None	None	N
I/V	0.1041	likely_benign	0.1016	benign	-1.785	Destabilizing	0.09	N	0.571	neutral	N	0.475901461	None	None	N
I/W	0.8081	likely_pathogenic	0.8471	pathogenic	-2.149	Highly Destabilizing	0.981	D	0.695	prob.neutral	None	None	None	None	N
I/Y	0.4964	ambiguous	0.5857	pathogenic	-1.922	Destabilizing	0.818	D	0.684	prob.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.