TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17818	53677;53678;53679	chr2:178607150;178607149;178607148	chr2:179471877;179471876;179471875
N2AB	16177	48754;48755;48756	chr2:178607150;178607149;178607148	chr2:179471877;179471876;179471875
N2A	15250	45973;45974;45975	chr2:178607150;178607149;178607148	chr2:179471877;179471876;179471875
N2B	8753	26482;26483;26484	chr2:178607150;178607149;178607148	chr2:179471877;179471876;179471875
Novex-1	8878	26857;26858;26859	chr2:178607150;178607149;178607148	chr2:179471877;179471876;179471875
Novex-2	8945	27058;27059;27060	chr2:178607150;178607149;178607148	chr2:179471877;179471876;179471875
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-17
• Domain position: 55
• Structural Position: 83
• Q(SASA): 0.6955
• 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
E/D	rs1055155891	None	0.001	N	0.134	0.059	0.0297737177859	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs1055155891	None	0.001	N	0.134	0.059	0.0297737177859	gnomAD-4.0.0	6.57964E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47184E-05	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
E/A	0.1715	likely_benign	0.2051	benign	-0.26	Destabilizing	0.003	N	0.165	neutral	N	0.384204808	None	None	N
E/C	0.8272	likely_pathogenic	0.897	pathogenic	-0.048	Destabilizing	0.981	D	0.287	neutral	None	None	None	None	N
E/D	0.1148	likely_benign	0.1315	benign	-0.286	Destabilizing	0.001	N	0.134	neutral	N	0.385319529	None	None	N
E/F	0.7968	likely_pathogenic	0.8281	pathogenic	-0.121	Destabilizing	0.932	D	0.293	neutral	None	None	None	None	N
E/G	0.1926	likely_benign	0.2159	benign	-0.437	Destabilizing	0.165	N	0.304	neutral	N	0.474344022	None	None	N
E/H	0.5691	likely_pathogenic	0.6491	pathogenic	0.226	Stabilizing	0.932	D	0.36	neutral	None	None	None	None	N
E/I	0.4154	ambiguous	0.4604	ambiguous	0.165	Stabilizing	0.818	D	0.339	neutral	None	None	None	None	N
E/K	0.2939	likely_benign	0.3122	benign	0.494	Stabilizing	0.324	N	0.262	neutral	N	0.397614035	None	None	N
E/L	0.4469	ambiguous	0.5032	ambiguous	0.165	Stabilizing	0.388	N	0.373	neutral	None	None	None	None	N
E/M	0.5307	ambiguous	0.5869	pathogenic	0.145	Stabilizing	0.981	D	0.287	neutral	None	None	None	None	N
E/N	0.2656	likely_benign	0.3235	benign	0.096	Stabilizing	0.241	N	0.337	neutral	None	None	None	None	N
E/P	0.3498	ambiguous	0.4325	ambiguous	0.043	Stabilizing	0.002	N	0.167	neutral	None	None	None	None	N
E/Q	0.1953	likely_benign	0.2264	benign	0.136	Stabilizing	0.324	N	0.336	neutral	N	0.435441705	None	None	N
E/R	0.4296	ambiguous	0.4824	ambiguous	0.689	Stabilizing	0.69	D	0.351	neutral	None	None	None	None	N
E/S	0.1914	likely_benign	0.2347	benign	-0.026	Destabilizing	0.116	N	0.273	neutral	None	None	None	None	N
E/T	0.2304	likely_benign	0.2671	benign	0.128	Stabilizing	0.388	N	0.339	neutral	None	None	None	None	N
E/V	0.2613	likely_benign	0.2809	benign	0.043	Stabilizing	0.324	N	0.322	neutral	N	0.434748271	None	None	N
E/W	0.9182	likely_pathogenic	0.9413	pathogenic	0.027	Stabilizing	0.981	D	0.465	neutral	None	None	None	None	N
E/Y	0.7062	likely_pathogenic	0.7611	pathogenic	0.13	Stabilizing	0.932	D	0.296	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.