TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27164	81715;81716;81717	chr2:178564642;178564641;178564640	chr2:179429369;179429368;179429367
N2AB	25523	76792;76793;76794	chr2:178564642;178564641;178564640	chr2:179429369;179429368;179429367
N2A	24596	74011;74012;74013	chr2:178564642;178564641;178564640	chr2:179429369;179429368;179429367
N2B	18099	54520;54521;54522	chr2:178564642;178564641;178564640	chr2:179429369;179429368;179429367
Novex-1	18224	54895;54896;54897	chr2:178564642;178564641;178564640	chr2:179429369;179429368;179429367
Novex-2	18291	55096;55097;55098	chr2:178564642;178564641;178564640	chr2:179429369;179429368;179429367
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-85
• Domain position: 93
• Structural Position: 126
• Q(SASA): 0.2526
• 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
C/R	None	None	None	N	0.299	0.23	0.474954162714	gnomAD-4.0.0	1.59187E-06	None	None	None	None	N	None	0	0	None	0	2.78056E-05	None	0	0	0	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
C/A	0.1793	likely_benign	0.1871	benign	-1.549	Destabilizing	0.013	N	0.188	neutral	None	None	None	None	N
C/D	0.4868	ambiguous	0.4982	ambiguous	0.033	Stabilizing	0.125	N	0.401	neutral	None	None	None	None	N
C/E	0.5927	likely_pathogenic	0.6177	pathogenic	0.104	Stabilizing	0.125	N	0.382	neutral	None	None	None	None	N
C/F	0.1495	likely_benign	0.1499	benign	-0.937	Destabilizing	0.207	N	0.591	neutral	N	0.442263316	None	None	N
C/G	0.0757	likely_benign	0.0784	benign	-1.826	Destabilizing	None	N	0.257	neutral	N	0.420256035	None	None	N
C/H	0.3242	likely_benign	0.343	ambiguous	-1.666	Destabilizing	0.711	D	0.535	neutral	None	None	None	None	N
C/I	0.2548	likely_benign	0.279	benign	-0.853	Destabilizing	0.067	N	0.326	neutral	None	None	None	None	N
C/K	0.5269	ambiguous	0.5633	ambiguous	-0.757	Destabilizing	0.03	N	0.358	neutral	None	None	None	None	N
C/L	0.2443	likely_benign	0.2707	benign	-0.853	Destabilizing	None	N	0.111	neutral	None	None	None	None	N
C/M	0.3886	ambiguous	0.4332	ambiguous	-0.069	Destabilizing	0.549	D	0.454	neutral	None	None	None	None	N
C/N	0.2171	likely_benign	0.2294	benign	-0.641	Destabilizing	0.125	N	0.399	neutral	None	None	None	None	N
C/P	0.2249	likely_benign	0.2476	benign	-1.059	Destabilizing	None	N	0.317	neutral	None	None	None	None	N
C/Q	0.3998	ambiguous	0.431	ambiguous	-0.611	Destabilizing	0.257	N	0.575	neutral	None	None	None	None	N
C/R	0.2848	likely_benign	0.3014	benign	-0.497	Destabilizing	None	N	0.299	neutral	N	0.441978101	None	None	N
C/S	0.1314	likely_benign	0.1347	benign	-1.236	Destabilizing	0.001	N	0.11	neutral	N	0.361727806	None	None	N
C/T	0.2331	likely_benign	0.2505	benign	-0.992	Destabilizing	0.03	N	0.312	neutral	None	None	None	None	N
C/V	0.2289	likely_benign	0.2442	benign	-1.059	Destabilizing	0.03	N	0.311	neutral	None	None	None	None	N
C/W	0.3956	ambiguous	0.406	ambiguous	-0.87	Destabilizing	0.955	D	0.488	neutral	N	0.482998004	None	None	N
C/Y	0.1712	likely_benign	0.1737	benign	-0.874	Destabilizing	0.347	N	0.625	neutral	N	0.4710875	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.