TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9635	29128;29129;29130	chr2:178707664;178707663;178707662	chr2:179572391;179572390;179572389
N2AB	9318	28177;28178;28179	chr2:178707664;178707663;178707662	chr2:179572391;179572390;179572389
N2A	8391	25396;25397;25398	chr2:178707664;178707663;178707662	chr2:179572391;179572390;179572389
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-82
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.6343
• 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
R/G	rs397517531	None	0.024	None	0.287	0.199	0.310458034454	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
R/G	rs397517531	None	0.024	None	0.287	0.199	0.310458034454	gnomAD-4.0.0	3.42088E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79882E-06	2.31884E-05	1.65645E-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
R/A	0.3156	likely_benign	0.2277	benign	-0.374	Destabilizing	0.016	N	0.281	neutral	None	None	None	None	N
R/C	0.2479	likely_benign	0.1834	benign	-0.216	Destabilizing	0.864	D	0.346	neutral	None	None	None	None	N
R/D	0.5518	ambiguous	0.4769	ambiguous	0.066	Stabilizing	0.038	N	0.332	neutral	None	None	None	None	N
R/E	0.3993	ambiguous	0.2968	benign	0.158	Stabilizing	0.016	N	0.279	neutral	None	None	None	None	N
R/F	0.5398	ambiguous	0.4321	ambiguous	-0.407	Destabilizing	0.356	N	0.379	neutral	None	None	None	None	N
R/G	0.1689	likely_benign	0.1307	benign	-0.645	Destabilizing	0.024	N	0.287	neutral	None	None	None	None	N
R/H	0.0949	likely_benign	0.0951	benign	-1.11	Destabilizing	0.356	N	0.329	neutral	None	None	None	None	N
R/I	0.27	likely_benign	0.2004	benign	0.33	Stabilizing	0.171	N	0.438	neutral	None	None	None	None	N
R/K	0.0976	likely_benign	0.0801	benign	-0.327	Destabilizing	None	N	0.099	neutral	None	None	None	None	N
R/L	0.2388	likely_benign	0.1901	benign	0.33	Stabilizing	0.038	N	0.327	neutral	None	None	None	None	N
R/M	0.2937	likely_benign	0.2117	benign	0.055	Stabilizing	0.628	D	0.367	neutral	None	None	None	None	N
R/N	0.4147	ambiguous	0.3481	ambiguous	0.216	Stabilizing	None	N	0.123	neutral	None	None	None	None	N
R/P	0.7184	likely_pathogenic	0.5811	pathogenic	0.117	Stabilizing	0.136	N	0.409	neutral	None	None	None	None	N
R/Q	0.1052	likely_benign	0.0942	benign	0.016	Stabilizing	0.038	N	0.258	neutral	None	None	None	None	N
R/S	0.335	likely_benign	0.2602	benign	-0.406	Destabilizing	0.001	N	0.215	neutral	None	None	None	None	N
R/T	0.1788	likely_benign	0.141	benign	-0.152	Destabilizing	0.001	N	0.225	neutral	None	None	None	None	N
R/V	0.3733	ambiguous	0.277	benign	0.117	Stabilizing	0.038	N	0.394	neutral	None	None	None	None	N
R/W	0.2435	likely_benign	0.1869	benign	-0.218	Destabilizing	0.864	D	0.391	neutral	None	None	None	None	N
R/Y	0.4177	ambiguous	0.344	ambiguous	0.136	Stabilizing	0.628	D	0.355	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.