TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18207	54844;54845;54846	chr2:178604068;178604067;178604066	chr2:179468795;179468794;179468793
N2AB	16566	49921;49922;49923	chr2:178604068;178604067;178604066	chr2:179468795;179468794;179468793
N2A	15639	47140;47141;47142	chr2:178604068;178604067;178604066	chr2:179468795;179468794;179468793
N2B	9142	27649;27650;27651	chr2:178604068;178604067;178604066	chr2:179468795;179468794;179468793
Novex-1	9267	28024;28025;28026	chr2:178604068;178604067;178604066	chr2:179468795;179468794;179468793
Novex-2	9334	28225;28226;28227	chr2:178604068;178604067;178604066	chr2:179468795;179468794;179468793
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-20
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.4622
• 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/K	None	None	0.016	N	0.237	0.26	0.31291088546	gnomAD-4.0.0	1.59316E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02755E-05

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	0.4595	ambiguous	0.3531	ambiguous	-0.804	Destabilizing	0.716	D	0.529	neutral	N	0.484423838	None	None	N
E/C	0.9584	likely_pathogenic	0.948	pathogenic	-0.42	Destabilizing	0.998	D	0.7	prob.neutral	None	None	None	None	N
E/D	0.4266	ambiguous	0.3614	ambiguous	-1.014	Destabilizing	0.834	D	0.397	neutral	N	0.492700497	None	None	N
E/F	0.9615	likely_pathogenic	0.936	pathogenic	-0.132	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
E/G	0.5252	ambiguous	0.4319	ambiguous	-1.163	Destabilizing	0.946	D	0.565	neutral	N	0.479348183	None	None	N
E/H	0.8958	likely_pathogenic	0.8445	pathogenic	-0.26	Destabilizing	0.994	D	0.584	neutral	None	None	None	None	N
E/I	0.7244	likely_pathogenic	0.6157	pathogenic	0.175	Stabilizing	0.979	D	0.74	deleterious	None	None	None	None	N
E/K	0.5865	likely_pathogenic	0.4872	ambiguous	-0.379	Destabilizing	0.016	N	0.237	neutral	N	0.50027983	None	None	N
E/L	0.7375	likely_pathogenic	0.6207	pathogenic	0.175	Stabilizing	0.959	D	0.693	prob.neutral	None	None	None	None	N
E/M	0.7674	likely_pathogenic	0.6803	pathogenic	0.532	Stabilizing	0.998	D	0.666	neutral	None	None	None	None	N
E/N	0.7425	likely_pathogenic	0.6702	pathogenic	-0.985	Destabilizing	0.959	D	0.589	neutral	None	None	None	None	N
E/P	0.7425	likely_pathogenic	0.7104	pathogenic	-0.13	Destabilizing	0.979	D	0.717	prob.delet.	None	None	None	None	N
E/Q	0.3711	ambiguous	0.3098	benign	-0.84	Destabilizing	0.716	D	0.537	neutral	D	0.522636615	None	None	N
E/R	0.7094	likely_pathogenic	0.6171	pathogenic	-0.043	Destabilizing	0.921	D	0.575	neutral	None	None	None	None	N
E/S	0.6359	likely_pathogenic	0.5311	ambiguous	-1.242	Destabilizing	0.769	D	0.512	neutral	None	None	None	None	N
E/T	0.6347	likely_pathogenic	0.5292	ambiguous	-0.934	Destabilizing	0.959	D	0.627	neutral	None	None	None	None	N
E/V	0.5213	ambiguous	0.4111	ambiguous	-0.13	Destabilizing	0.946	D	0.677	prob.neutral	N	0.480335688	None	None	N
E/W	0.9846	likely_pathogenic	0.974	pathogenic	0.185	Stabilizing	0.998	D	0.701	prob.neutral	None	None	None	None	N
E/Y	0.9423	likely_pathogenic	0.915	pathogenic	0.147	Stabilizing	0.993	D	0.695	prob.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.