TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30657	92194;92195;92196	chr2:178549753;178549752;178549751	chr2:179414480;179414479;179414478
N2AB	29016	87271;87272;87273	chr2:178549753;178549752;178549751	chr2:179414480;179414479;179414478
N2A	28089	84490;84491;84492	chr2:178549753;178549752;178549751	chr2:179414480;179414479;179414478
N2B	21592	64999;65000;65001	chr2:178549753;178549752;178549751	chr2:179414480;179414479;179414478
Novex-1	21717	65374;65375;65376	chr2:178549753;178549752;178549751	chr2:179414480;179414479;179414478
Novex-2	21784	65575;65576;65577	chr2:178549753;178549752;178549751	chr2:179414480;179414479;179414478
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-111
• Domain position: 39
• Structural Position: 40
• Q(SASA): 0.0656
• 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
I/M	rs888042945	None	0.984	N	0.618	0.412	0.497613835824	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
I/M	rs888042945	None	0.984	N	0.618	0.412	0.497613835824	gnomAD-4.0.0	2.73696E-06	None	None	None	None	N	None	0	8.94574E-05	None	0	0	None	0	0	0	0	0
I/T	rs942083769	-3.559	0.896	D	0.601	0.492	0.730582074568	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
I/T	rs942083769	-3.559	0.896	D	0.601	0.492	0.730582074568	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	6.55E-05	0	0	0	None	0	0	0	0	0
I/T	rs942083769	-3.559	0.896	D	0.601	0.492	0.730582074568	gnomAD-4.0.0	4.33805E-06	None	None	None	None	N	None	1.33501E-05	1.66717E-05	None	0	0	None	0	0	2.54291E-06	1.09803E-05	1.60123E-05
I/V	rs940922600	-2.151	0.004	N	0.185	0.072	0.361160317528	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
I/V	rs940922600	-2.151	0.004	N	0.185	0.072	0.361160317528	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs940922600	-2.151	0.004	N	0.185	0.072	0.361160317528	gnomAD-4.0.0	2.56235E-06	None	None	None	None	N	None	3.38295E-05	0	None	0	0	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
I/A	0.8171	likely_pathogenic	0.858	pathogenic	-3.004	Highly Destabilizing	0.702	D	0.645	neutral	None	None	None	None	N
I/C	0.9518	likely_pathogenic	0.9572	pathogenic	-1.982	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
I/D	0.9993	likely_pathogenic	0.9995	pathogenic	-3.597	Highly Destabilizing	0.996	D	0.859	deleterious	None	None	None	None	N
I/E	0.9971	likely_pathogenic	0.9977	pathogenic	-3.273	Highly Destabilizing	0.988	D	0.838	deleterious	None	None	None	None	N
I/F	0.7318	likely_pathogenic	0.8298	pathogenic	-1.761	Destabilizing	0.968	D	0.622	neutral	D	0.53069625	None	None	N
I/G	0.9894	likely_pathogenic	0.9926	pathogenic	-3.594	Highly Destabilizing	0.988	D	0.804	deleterious	None	None	None	None	N
I/H	0.9965	likely_pathogenic	0.9977	pathogenic	-3.223	Highly Destabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
I/K	0.9924	likely_pathogenic	0.9945	pathogenic	-2.278	Highly Destabilizing	0.988	D	0.841	deleterious	None	None	None	None	N
I/L	0.1868	likely_benign	0.1879	benign	-1.208	Destabilizing	0.437	N	0.303	neutral	N	0.449701868	None	None	N
I/M	0.2977	likely_benign	0.3328	benign	-1.374	Destabilizing	0.984	D	0.618	neutral	N	0.494398835	None	None	N
I/N	0.9911	likely_pathogenic	0.9929	pathogenic	-2.999	Highly Destabilizing	0.995	D	0.873	deleterious	D	0.53094974	None	None	N
I/P	0.9926	likely_pathogenic	0.9952	pathogenic	-1.801	Destabilizing	0.996	D	0.863	deleterious	None	None	None	None	N
I/Q	0.9936	likely_pathogenic	0.9952	pathogenic	-2.635	Highly Destabilizing	0.996	D	0.88	deleterious	None	None	None	None	N
I/R	0.9872	likely_pathogenic	0.9908	pathogenic	-2.31	Highly Destabilizing	0.988	D	0.871	deleterious	None	None	None	None	N
I/S	0.9672	likely_pathogenic	0.9762	pathogenic	-3.5	Highly Destabilizing	0.984	D	0.764	deleterious	D	0.53094974	None	None	N
I/T	0.755	likely_pathogenic	0.8176	pathogenic	-3.021	Highly Destabilizing	0.896	D	0.601	neutral	D	0.53069625	None	None	N
I/V	0.0845	likely_benign	0.0959	benign	-1.801	Destabilizing	0.004	N	0.185	neutral	N	0.392914718	None	None	N
I/W	0.9944	likely_pathogenic	0.9968	pathogenic	-2.124	Highly Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
I/Y	0.986	likely_pathogenic	0.9912	pathogenic	-1.996	Destabilizing	0.988	D	0.742	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.