TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9387	28384;28385;28386	chr2:178711077;178711076;178711075	chr2:179575804;179575803;179575802
N2AB	9070	27433;27434;27435	chr2:178711077;178711076;178711075	chr2:179575804;179575803;179575802
N2A	8143	24652;24653;24654	chr2:178711077;178711076;178711075	chr2:179575804;179575803;179575802
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: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-79
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.5096
• 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/S	None	None	0.012	None	0.405	0.077	0.18274738541	gnomAD-4.0.0	1.65249E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.95098E-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
R/A	0.3502	ambiguous	0.36	ambiguous	-0.478	Destabilizing	0.016	N	0.401	neutral	None	None	None	None	N
R/C	0.3248	likely_benign	0.2961	benign	-0.454	Destabilizing	0.864	D	0.496	neutral	None	None	None	None	N
R/D	0.6532	likely_pathogenic	0.6692	pathogenic	0.032	Stabilizing	0.016	N	0.467	neutral	None	None	None	None	N
R/E	0.3546	ambiguous	0.3749	ambiguous	0.13	Stabilizing	0.016	N	0.367	neutral	None	None	None	None	N
R/F	0.5021	ambiguous	0.4999	ambiguous	-0.469	Destabilizing	0.628	D	0.497	neutral	None	None	None	None	N
R/G	0.2729	likely_benign	0.2922	benign	-0.749	Destabilizing	0.024	N	0.435	neutral	None	None	None	None	N
R/H	0.1085	likely_benign	0.1123	benign	-1.102	Destabilizing	0.356	N	0.517	neutral	None	None	None	None	N
R/I	0.2606	likely_benign	0.2739	benign	0.226	Stabilizing	0.356	N	0.537	neutral	None	None	None	None	N
R/K	0.0789	likely_benign	0.0856	benign	-0.48	Destabilizing	None	N	0.171	neutral	None	None	None	None	N
R/L	0.2199	likely_benign	0.2339	benign	0.226	Stabilizing	0.031	N	0.483	neutral	None	None	None	None	N
R/M	0.2367	likely_benign	0.2493	benign	-0.112	Destabilizing	0.56	D	0.525	neutral	None	None	None	None	N
R/N	0.4356	ambiguous	0.4392	ambiguous	0.002	Stabilizing	None	N	0.191	neutral	None	None	None	None	N
R/P	0.7543	likely_pathogenic	0.8017	pathogenic	0.013	Stabilizing	0.136	N	0.543	neutral	None	None	None	None	N
R/Q	0.1072	likely_benign	0.1122	benign	-0.181	Destabilizing	0.038	N	0.455	neutral	None	None	None	None	N
R/S	0.3672	ambiguous	0.3652	ambiguous	-0.655	Destabilizing	0.012	N	0.405	neutral	None	None	None	None	N
R/T	0.1901	likely_benign	0.1932	benign	-0.391	Destabilizing	0.024	N	0.463	neutral	None	None	None	None	N
R/V	0.3317	likely_benign	0.3485	ambiguous	0.013	Stabilizing	0.072	N	0.529	neutral	None	None	None	None	N
R/W	0.2017	likely_benign	0.2121	benign	-0.251	Destabilizing	0.828	D	0.513	neutral	None	None	None	None	N
R/Y	0.3946	ambiguous	0.3821	ambiguous	0.085	Stabilizing	0.628	D	0.503	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.