TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27331	82216;82217;82218	chr2:178564141;178564140;178564139	chr2:179428868;179428867;179428866
N2AB	25690	77293;77294;77295	chr2:178564141;178564140;178564139	chr2:179428868;179428867;179428866
N2A	24763	74512;74513;74514	chr2:178564141;178564140;178564139	chr2:179428868;179428867;179428866
N2B	18266	55021;55022;55023	chr2:178564141;178564140;178564139	chr2:179428868;179428867;179428866
Novex-1	18391	55396;55397;55398	chr2:178564141;178564140;178564139	chr2:179428868;179428867;179428866
Novex-2	18458	55597;55598;55599	chr2:178564141;178564140;178564139	chr2:179428868;179428867;179428866
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-140
• Domain position: 54
• Structural Position: 135
• Q(SASA): 0.3287
• 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
K/N	None	None	0.002	N	0.284	0.127	0.0986583533028	gnomAD-4.0.0	1.5913E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
K/A	0.282	likely_benign	0.3112	benign	-0.347	Destabilizing	0.067	N	0.491	neutral	None	None	None	None	N
K/C	0.4508	ambiguous	0.5104	ambiguous	-0.756	Destabilizing	0.935	D	0.599	neutral	None	None	None	None	N
K/D	0.4705	ambiguous	0.4966	ambiguous	-0.869	Destabilizing	0.081	N	0.523	neutral	None	None	None	None	N
K/E	0.1585	likely_benign	0.1686	benign	-0.819	Destabilizing	0.027	N	0.48	neutral	N	0.496135952	None	None	N
K/F	0.5998	likely_pathogenic	0.6367	pathogenic	-0.597	Destabilizing	0.555	D	0.599	neutral	None	None	None	None	N
K/G	0.3541	ambiguous	0.3819	ambiguous	-0.625	Destabilizing	0.149	N	0.528	neutral	None	None	None	None	N
K/H	0.185	likely_benign	0.1972	benign	-1.11	Destabilizing	0.001	N	0.276	neutral	None	None	None	None	N
K/I	0.305	likely_benign	0.3462	ambiguous	0.335	Stabilizing	0.484	N	0.61	neutral	N	0.494058439	None	None	N
K/L	0.2894	likely_benign	0.3195	benign	0.335	Stabilizing	0.149	N	0.553	neutral	None	None	None	None	N
K/M	0.1639	likely_benign	0.1832	benign	0.416	Stabilizing	0.935	D	0.575	neutral	None	None	None	None	N
K/N	0.2476	likely_benign	0.2657	benign	-0.512	Destabilizing	0.002	N	0.284	neutral	N	0.465583758	None	None	N
K/P	0.9165	likely_pathogenic	0.9159	pathogenic	0.137	Stabilizing	0.555	D	0.604	neutral	None	None	None	None	N
K/Q	0.104	likely_benign	0.1104	benign	-0.818	Destabilizing	0.117	N	0.498	neutral	N	0.49734946	None	None	N
K/R	0.0716	likely_benign	0.0728	benign	-0.352	Destabilizing	None	N	0.112	neutral	N	0.43048975	None	None	N
K/S	0.2735	likely_benign	0.2953	benign	-1.016	Destabilizing	0.149	N	0.449	neutral	None	None	None	None	N
K/T	0.1241	likely_benign	0.1336	benign	-0.798	Destabilizing	0.117	N	0.507	neutral	N	0.433279339	None	None	N
K/V	0.2833	likely_benign	0.3163	benign	0.137	Stabilizing	0.38	N	0.583	neutral	None	None	None	None	N
K/W	0.56	ambiguous	0.6186	pathogenic	-0.549	Destabilizing	0.935	D	0.627	neutral	None	None	None	None	N
K/Y	0.4028	ambiguous	0.4408	ambiguous	-0.103	Destabilizing	0.38	N	0.605	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.