TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22304	67135;67136;67137	chr2:178580469;178580468;178580467	chr2:179445196;179445195;179445194
N2AB	20663	62212;62213;62214	chr2:178580469;178580468;178580467	chr2:179445196;179445195;179445194
N2A	19736	59431;59432;59433	chr2:178580469;178580468;178580467	chr2:179445196;179445195;179445194
N2B	13239	39940;39941;39942	chr2:178580469;178580468;178580467	chr2:179445196;179445195;179445194
Novex-1	13364	40315;40316;40317	chr2:178580469;178580468;178580467	chr2:179445196;179445195;179445194
Novex-2	13431	40516;40517;40518	chr2:178580469;178580468;178580467	chr2:179445196;179445195;179445194
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-126
• Domain position: 40
• Structural Position: 70
• Q(SASA): 0.3535
• 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
D/N	None	None	0.334	N	0.421	0.198	0.292062946507	gnomAD-4.0.0	1.59281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86076E-06	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
D/A	0.287	likely_benign	0.273	benign	-0.033	Destabilizing	0.201	N	0.476	neutral	N	0.47585668	None	None	N
D/C	0.7576	likely_pathogenic	0.757	pathogenic	0.001	Stabilizing	0.982	D	0.674	neutral	None	None	None	None	N
D/E	0.1067	likely_benign	0.1048	benign	-0.209	Destabilizing	0.001	N	0.257	neutral	N	0.411805202	None	None	N
D/F	0.7961	likely_pathogenic	0.7923	pathogenic	-0.107	Destabilizing	0.935	D	0.687	prob.neutral	None	None	None	None	N
D/G	0.2307	likely_benign	0.2196	benign	-0.166	Destabilizing	0.334	N	0.439	neutral	N	0.487132466	None	None	N
D/H	0.4484	ambiguous	0.415	ambiguous	0.336	Stabilizing	0.931	D	0.551	neutral	N	0.519263528	None	None	N
D/I	0.6099	likely_pathogenic	0.6024	pathogenic	0.252	Stabilizing	0.826	D	0.697	prob.neutral	None	None	None	None	N
D/K	0.4613	ambiguous	0.4471	ambiguous	0.457	Stabilizing	0.25	N	0.407	neutral	None	None	None	None	N
D/L	0.5226	ambiguous	0.5315	ambiguous	0.252	Stabilizing	0.7	D	0.687	prob.neutral	None	None	None	None	N
D/M	0.7209	likely_pathogenic	0.7162	pathogenic	0.168	Stabilizing	0.982	D	0.679	prob.neutral	None	None	None	None	N
D/N	0.1454	likely_benign	0.1422	benign	0.235	Stabilizing	0.334	N	0.421	neutral	N	0.439301234	None	None	N
D/P	0.8039	likely_pathogenic	0.7733	pathogenic	0.177	Stabilizing	0.826	D	0.529	neutral	None	None	None	None	N
D/Q	0.3574	ambiguous	0.3438	ambiguous	0.248	Stabilizing	0.539	D	0.417	neutral	None	None	None	None	N
D/R	0.5792	likely_pathogenic	0.5552	ambiguous	0.634	Stabilizing	0.539	D	0.627	neutral	None	None	None	None	N
D/S	0.1916	likely_benign	0.1827	benign	0.135	Stabilizing	0.25	N	0.387	neutral	None	None	None	None	N
D/T	0.3555	ambiguous	0.34	ambiguous	0.242	Stabilizing	0.7	D	0.439	neutral	None	None	None	None	N
D/V	0.3986	ambiguous	0.3853	ambiguous	0.177	Stabilizing	0.638	D	0.679	prob.neutral	N	0.481571931	None	None	N
D/W	0.9112	likely_pathogenic	0.8981	pathogenic	-0.055	Destabilizing	0.982	D	0.674	neutral	None	None	None	None	N
D/Y	0.4017	ambiguous	0.3915	ambiguous	0.117	Stabilizing	0.916	D	0.687	prob.neutral	N	0.483833132	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.