TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28263	85012;85013;85014	chr2:178561345;178561344;178561343	chr2:179426072;179426071;179426070
N2AB	26622	80089;80090;80091	chr2:178561345;178561344;178561343	chr2:179426072;179426071;179426070
N2A	25695	77308;77309;77310	chr2:178561345;178561344;178561343	chr2:179426072;179426071;179426070
N2B	19198	57817;57818;57819	chr2:178561345;178561344;178561343	chr2:179426072;179426071;179426070
Novex-1	19323	58192;58193;58194	chr2:178561345;178561344;178561343	chr2:179426072;179426071;179426070
Novex-2	19390	58393;58394;58395	chr2:178561345;178561344;178561343	chr2:179426072;179426071;179426070
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-94
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.5552
• 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
N/D	rs762665595	0.457	0.067	N	0.265	0.107	0.126345400529	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	7.32654E-05
N/Y	rs762665595	-0.433	0.998	N	0.599	0.413	0.535152128566	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	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
N/A	0.202	likely_benign	0.2079	benign	-0.599	Destabilizing	0.968	D	0.534	neutral	None	None	None	None	N
N/C	0.292	likely_benign	0.3072	benign	0.249	Stabilizing	1.0	D	0.634	neutral	None	None	None	None	N
N/D	0.1497	likely_benign	0.1474	benign	-0.281	Destabilizing	0.067	N	0.265	neutral	N	0.442039603	None	None	N
N/E	0.4291	ambiguous	0.4322	ambiguous	-0.278	Destabilizing	0.938	D	0.433	neutral	None	None	None	None	N
N/F	0.5799	likely_pathogenic	0.583	pathogenic	-0.787	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
N/G	0.2908	likely_benign	0.2878	benign	-0.833	Destabilizing	0.968	D	0.399	neutral	None	None	None	None	N
N/H	0.1149	likely_benign	0.113	benign	-0.836	Destabilizing	0.998	D	0.577	neutral	N	0.472257838	None	None	N
N/I	0.3106	likely_benign	0.3319	benign	-0.05	Destabilizing	0.994	D	0.681	prob.neutral	N	0.468979382	None	None	N
N/K	0.4142	ambiguous	0.4032	ambiguous	-0.02	Destabilizing	0.958	D	0.537	neutral	N	0.501954698	None	None	N
N/L	0.3316	likely_benign	0.3381	benign	-0.05	Destabilizing	0.995	D	0.665	neutral	None	None	None	None	N
N/M	0.3977	ambiguous	0.4053	ambiguous	0.51	Stabilizing	1.0	D	0.563	neutral	None	None	None	None	N
N/P	0.9658	likely_pathogenic	0.9706	pathogenic	-0.205	Destabilizing	0.995	D	0.609	neutral	None	None	None	None	N
N/Q	0.3861	ambiguous	0.3835	ambiguous	-0.637	Destabilizing	0.995	D	0.601	neutral	None	None	None	None	N
N/R	0.3851	ambiguous	0.3689	ambiguous	0.051	Stabilizing	0.995	D	0.609	neutral	None	None	None	None	N
N/S	0.08	likely_benign	0.0829	benign	-0.401	Destabilizing	0.958	D	0.399	neutral	N	0.446157344	None	None	N
N/T	0.1518	likely_benign	0.1609	benign	-0.234	Destabilizing	0.958	D	0.515	neutral	N	0.475763331	None	None	N
N/V	0.2517	likely_benign	0.2655	benign	-0.205	Destabilizing	0.995	D	0.661	neutral	None	None	None	None	N
N/W	0.8037	likely_pathogenic	0.8198	pathogenic	-0.64	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
N/Y	0.2087	likely_benign	0.2107	benign	-0.407	Destabilizing	0.998	D	0.599	neutral	N	0.495135033	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.