TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2883	8872;8873;8874	chr2:178769934;178769933;178769932	chr2:179634661;179634660;179634659
N2AB	2883	8872;8873;8874	chr2:178769934;178769933;178769932	chr2:179634661;179634660;179634659
N2A	2883	8872;8873;8874	chr2:178769934;178769933;178769932	chr2:179634661;179634660;179634659
N2B	2837	8734;8735;8736	chr2:178769934;178769933;178769932	chr2:179634661;179634660;179634659
Novex-1	2837	8734;8735;8736	chr2:178769934;178769933;178769932	chr2:179634661;179634660;179634659
Novex-2	2837	8734;8735;8736	chr2:178769934;178769933;178769932	chr2:179634661;179634660;179634659
Novex-3	2883	8872;8873;8874	chr2:178769934;178769933;178769932	chr2:179634661;179634660;179634659

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-19
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.2571
• 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/Q	rs763935915	0.374	0.029	N	0.159	0.285	0.119812018005	gnomAD-2.1.1	2.79E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.28654E-04	None	0	0	0
H/Q	rs763935915	0.374	0.029	N	0.159	0.285	0.119812018005	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06868E-04	0
H/Q	rs763935915	0.374	0.029	N	0.159	0.285	0.119812018005	gnomAD-4.0.0	9.2936E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.64672E-04	0
H/R	rs753833148	-0.489	0.002	N	0.143	0.298	0.15556083564	gnomAD-2.1.1	2E-05	None	None	None	None	N	None	0	1.15781E-04	None	0	5.45E-05	None	0	None	0	0	0
H/R	rs753833148	-0.489	0.002	N	0.143	0.298	0.15556083564	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	6.54E-05	0	0	0	None	0	0	1.47E-05	2.07125E-04	0
H/R	rs753833148	-0.489	0.002	N	0.143	0.298	0.15556083564	gnomAD-4.0.0	1.3011E-05	None	None	None	None	N	None	0	1.16667E-04	None	0	4.45653E-05	None	0	0	2.54235E-06	5.48944E-05	6.40123E-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
H/A	0.4884	ambiguous	0.493	ambiguous	0.376	Stabilizing	0.495	N	0.233	neutral	None	None	None	None	N
H/C	0.2581	likely_benign	0.2567	benign	0.98	Stabilizing	0.995	D	0.228	neutral	None	None	None	None	N
H/D	0.4777	ambiguous	0.4802	ambiguous	0.038	Stabilizing	0.27	N	0.269	neutral	N	0.507795386	None	None	N
H/E	0.4498	ambiguous	0.4398	ambiguous	0.074	Stabilizing	0.329	N	0.199	neutral	None	None	None	None	N
H/F	0.4952	ambiguous	0.5148	ambiguous	1.091	Stabilizing	0.981	D	0.282	neutral	None	None	None	None	N
H/G	0.5669	likely_pathogenic	0.571	pathogenic	0.067	Stabilizing	0.329	N	0.265	neutral	None	None	None	None	N
H/I	0.5339	ambiguous	0.5185	ambiguous	1.172	Stabilizing	0.981	D	0.291	neutral	None	None	None	None	N
H/K	0.2623	likely_benign	0.2542	benign	0.377	Stabilizing	0.329	N	0.231	neutral	None	None	None	None	N
H/L	0.2328	likely_benign	0.236	benign	1.172	Stabilizing	0.642	D	0.308	neutral	N	0.504959425	None	None	N
H/M	0.6409	likely_pathogenic	0.6534	pathogenic	0.951	Stabilizing	0.981	D	0.231	neutral	None	None	None	None	N
H/N	0.1886	likely_benign	0.1877	benign	0.42	Stabilizing	0.002	N	0.145	neutral	N	0.507964228	None	None	N
H/P	0.6305	likely_pathogenic	0.5997	pathogenic	0.933	Stabilizing	0.917	D	0.305	neutral	N	0.508176519	None	None	N
H/Q	0.2208	likely_benign	0.2204	benign	0.551	Stabilizing	0.029	N	0.159	neutral	N	0.432118711	None	None	N
H/R	0.1061	likely_benign	0.1024	benign	-0.32	Destabilizing	0.002	N	0.143	neutral	N	0.393151679	None	None	N
H/S	0.4058	ambiguous	0.4162	ambiguous	0.562	Stabilizing	0.329	N	0.305	neutral	None	None	None	None	N
H/T	0.4233	ambiguous	0.4176	ambiguous	0.698	Stabilizing	0.704	D	0.297	neutral	None	None	None	None	N
H/V	0.4229	ambiguous	0.4204	ambiguous	0.933	Stabilizing	0.828	D	0.341	neutral	None	None	None	None	N
H/W	0.6218	likely_pathogenic	0.6519	pathogenic	1.081	Stabilizing	0.995	D	0.233	neutral	None	None	None	None	N
H/Y	0.1821	likely_benign	0.1833	benign	1.368	Stabilizing	0.917	D	0.277	neutral	N	0.499920769	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.