TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18123	54592;54593;54594	chr2:178604722;178604721;178604720	chr2:179469449;179469448;179469447
N2AB	16482	49669;49670;49671	chr2:178604722;178604721;178604720	chr2:179469449;179469448;179469447
N2A	15555	46888;46889;46890	chr2:178604722;178604721;178604720	chr2:179469449;179469448;179469447
N2B	9058	27397;27398;27399	chr2:178604722;178604721;178604720	chr2:179469449;179469448;179469447
Novex-1	9183	27772;27773;27774	chr2:178604722;178604721;178604720	chr2:179469449;179469448;179469447
Novex-2	9250	27973;27974;27975	chr2:178604722;178604721;178604720	chr2:179469449;179469448;179469447
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-19
• Domain position: 59
• Structural Position: 88
• Q(SASA): 0.1937
• 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/Q	None	None	0.638	N	0.533	0.234	0.184867976434	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
E/A	0.3689	ambiguous	0.3798	ambiguous	-0.172	Destabilizing	0.334	N	0.499	neutral	N	0.457510488	None	None	N
E/C	0.9314	likely_pathogenic	0.9415	pathogenic	-0.421	Destabilizing	0.982	D	0.651	neutral	None	None	None	None	N
E/D	0.155	likely_benign	0.1764	benign	-0.348	Destabilizing	0.001	N	0.148	neutral	N	0.398542329	None	None	N
E/F	0.9139	likely_pathogenic	0.9241	pathogenic	0.157	Stabilizing	0.982	D	0.67	neutral	None	None	None	None	N
E/G	0.2946	likely_benign	0.3191	benign	-0.377	Destabilizing	0.334	N	0.522	neutral	N	0.446834921	None	None	N
E/H	0.7609	likely_pathogenic	0.7721	pathogenic	0.685	Stabilizing	0.947	D	0.555	neutral	None	None	None	None	N
E/I	0.7369	likely_pathogenic	0.7684	pathogenic	0.34	Stabilizing	0.826	D	0.691	prob.neutral	None	None	None	None	N
E/K	0.4729	ambiguous	0.4699	ambiguous	0.23	Stabilizing	0.334	N	0.419	neutral	N	0.447256209	None	None	N
E/L	0.707	likely_pathogenic	0.7293	pathogenic	0.34	Stabilizing	0.826	D	0.689	prob.neutral	None	None	None	None	N
E/M	0.768	likely_pathogenic	0.7911	pathogenic	0.059	Stabilizing	0.982	D	0.641	neutral	None	None	None	None	N
E/N	0.4338	ambiguous	0.4951	ambiguous	-0.262	Destabilizing	0.25	N	0.491	neutral	None	None	None	None	N
E/P	0.8556	likely_pathogenic	0.8943	pathogenic	0.189	Stabilizing	0.826	D	0.645	neutral	None	None	None	None	N
E/Q	0.296	likely_benign	0.2908	benign	-0.18	Destabilizing	0.638	D	0.533	neutral	N	0.449488437	None	None	N
E/R	0.5956	likely_pathogenic	0.6067	pathogenic	0.631	Stabilizing	0.7	D	0.573	neutral	None	None	None	None	N
E/S	0.3809	ambiguous	0.4355	ambiguous	-0.415	Destabilizing	0.25	N	0.409	neutral	None	None	None	None	N
E/T	0.4732	ambiguous	0.5174	ambiguous	-0.231	Destabilizing	0.7	D	0.588	neutral	None	None	None	None	N
E/V	0.5275	ambiguous	0.5422	ambiguous	0.189	Stabilizing	0.781	D	0.66	neutral	N	0.472269296	None	None	N
E/W	0.9596	likely_pathogenic	0.9612	pathogenic	0.319	Stabilizing	0.982	D	0.657	neutral	None	None	None	None	N
E/Y	0.8318	likely_pathogenic	0.8462	pathogenic	0.403	Stabilizing	0.935	D	0.647	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.