TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30973	93142;93143;93144	chr2:178548709;178548708;178548707	chr2:179413436;179413435;179413434
N2AB	29332	88219;88220;88221	chr2:178548709;178548708;178548707	chr2:179413436;179413435;179413434
N2A	28405	85438;85439;85440	chr2:178548709;178548708;178548707	chr2:179413436;179413435;179413434
N2B	21908	65947;65948;65949	chr2:178548709;178548708;178548707	chr2:179413436;179413435;179413434
Novex-1	22033	66322;66323;66324	chr2:178548709;178548708;178548707	chr2:179413436;179413435;179413434
Novex-2	22100	66523;66524;66525	chr2:178548709;178548708;178548707	chr2:179413436;179413435;179413434
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-150
• Domain position: 47
• Structural Position: 125
• Q(SASA): 0.6101
• 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
H/P	None	None	0.784	N	0.421	0.285	0.427254322456	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
H/Q	rs765351582	0.416	0.01	N	0.165	0.122	0.0920862733494	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
H/Q	rs765351582	0.416	0.01	N	0.165	0.122	0.0920862733494	gnomAD-4.0.0	6.84188E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99454E-07	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
H/A	0.2676	likely_benign	0.2675	benign	-0.128	Destabilizing	0.176	N	0.282	neutral	None	None	None	None	N
H/C	0.1896	likely_benign	0.1942	benign	0.253	Stabilizing	0.995	D	0.332	neutral	None	None	None	None	N
H/D	0.2063	likely_benign	0.211	benign	0.142	Stabilizing	0.27	N	0.311	neutral	N	0.35914694	None	None	N
H/E	0.2418	likely_benign	0.2592	benign	0.177	Stabilizing	0.329	N	0.191	neutral	None	None	None	None	N
H/F	0.3164	likely_benign	0.3024	benign	0.56	Stabilizing	0.981	D	0.381	neutral	None	None	None	None	N
H/G	0.3854	ambiguous	0.3887	ambiguous	-0.408	Destabilizing	0.495	N	0.299	neutral	None	None	None	None	N
H/I	0.2529	likely_benign	0.2463	benign	0.591	Stabilizing	0.704	D	0.432	neutral	None	None	None	None	N
H/K	0.2284	likely_benign	0.2321	benign	-0.059	Destabilizing	0.329	N	0.306	neutral	None	None	None	None	N
H/L	0.1294	likely_benign	0.1258	benign	0.591	Stabilizing	0.425	N	0.375	neutral	N	0.412634708	None	None	N
H/M	0.412	ambiguous	0.4013	ambiguous	0.397	Stabilizing	0.944	D	0.343	neutral	None	None	None	None	N
H/N	0.0977	likely_benign	0.0974	benign	-0.074	Destabilizing	0.01	N	0.149	neutral	N	0.428161521	None	None	N
H/P	0.6399	likely_pathogenic	0.6744	pathogenic	0.375	Stabilizing	0.784	D	0.421	neutral	N	0.465853117	None	None	N
H/Q	0.1406	likely_benign	0.1468	benign	0.027	Stabilizing	0.01	N	0.165	neutral	N	0.421272834	None	None	N
H/R	0.1072	likely_benign	0.1117	benign	-0.442	Destabilizing	0.473	N	0.179	neutral	N	0.393355514	None	None	N
H/S	0.1948	likely_benign	0.1931	benign	-0.172	Destabilizing	0.037	N	0.185	neutral	None	None	None	None	N
H/T	0.2133	likely_benign	0.2103	benign	-0.032	Destabilizing	0.013	N	0.199	neutral	None	None	None	None	N
H/V	0.2076	likely_benign	0.2054	benign	0.375	Stabilizing	0.704	D	0.398	neutral	None	None	None	None	N
H/W	0.4787	ambiguous	0.4733	ambiguous	0.667	Stabilizing	0.995	D	0.337	neutral	None	None	None	None	N
H/Y	0.1182	likely_benign	0.1171	benign	0.912	Stabilizing	0.917	D	0.29	neutral	N	0.447440715	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.