TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30385	91378;91379;91380	chr2:178551747;178551746;178551745	chr2:179416474;179416473;179416472
N2AB	28744	86455;86456;86457	chr2:178551747;178551746;178551745	chr2:179416474;179416473;179416472
N2A	27817	83674;83675;83676	chr2:178551747;178551746;178551745	chr2:179416474;179416473;179416472
N2B	21320	64183;64184;64185	chr2:178551747;178551746;178551745	chr2:179416474;179416473;179416472
Novex-1	21445	64558;64559;64560	chr2:178551747;178551746;178551745	chr2:179416474;179416473;179416472
Novex-2	21512	64759;64760;64761	chr2:178551747;178551746;178551745	chr2:179416474;179416473;179416472
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-109
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.4907
• 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
R/T	rs780885701	-0.431	1.0	N	0.77	0.396	0.389126455913	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	1.11383E-04	None	0	None	0	0	0
R/T	rs780885701	-0.431	1.0	N	0.77	0.396	0.389126455913	gnomAD-4.0.0	3.18249E-06	None	None	None	None	N	None	0	0	None	0	5.54631E-05	None	0	0	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
R/A	0.799	likely_pathogenic	0.7734	pathogenic	-1.45	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
R/C	0.3367	likely_benign	0.3154	benign	-1.499	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
R/D	0.9457	likely_pathogenic	0.9329	pathogenic	-0.542	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
R/E	0.7638	likely_pathogenic	0.7238	pathogenic	-0.416	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
R/F	0.7632	likely_pathogenic	0.7295	pathogenic	-1.405	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
R/G	0.7377	likely_pathogenic	0.721	pathogenic	-1.745	Destabilizing	1.0	D	0.749	deleterious	N	0.478041055	None	None	N
R/H	0.169	likely_benign	0.1462	benign	-1.866	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
R/I	0.5161	ambiguous	0.4613	ambiguous	-0.643	Destabilizing	1.0	D	0.805	deleterious	N	0.511726188	None	None	N
R/K	0.1637	likely_benign	0.1459	benign	-1.437	Destabilizing	0.997	D	0.521	neutral	N	0.424376562	None	None	N
R/L	0.4699	ambiguous	0.4271	ambiguous	-0.643	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
R/M	0.5716	likely_pathogenic	0.515	ambiguous	-0.808	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
R/N	0.8938	likely_pathogenic	0.875	pathogenic	-0.905	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
R/P	0.9018	likely_pathogenic	0.8876	pathogenic	-0.894	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
R/Q	0.1926	likely_benign	0.1757	benign	-1.135	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
R/S	0.851	likely_pathogenic	0.8362	pathogenic	-1.82	Destabilizing	1.0	D	0.777	deleterious	N	0.472399795	None	None	N
R/T	0.6057	likely_pathogenic	0.5381	ambiguous	-1.511	Destabilizing	1.0	D	0.77	deleterious	N	0.431278318	None	None	N
R/V	0.6077	likely_pathogenic	0.5558	ambiguous	-0.894	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
R/W	0.3217	likely_benign	0.2901	benign	-0.966	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
R/Y	0.598	likely_pathogenic	0.5578	ambiguous	-0.684	Destabilizing	1.0	D	0.811	deleterious	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.