TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18116	54571;54572;54573	chr2:178604743;178604742;178604741	chr2:179469470;179469469;179469468
N2AB	16475	49648;49649;49650	chr2:178604743;178604742;178604741	chr2:179469470;179469469;179469468
N2A	15548	46867;46868;46869	chr2:178604743;178604742;178604741	chr2:179469470;179469469;179469468
N2B	9051	27376;27377;27378	chr2:178604743;178604742;178604741	chr2:179469470;179469469;179469468
Novex-1	9176	27751;27752;27753	chr2:178604743;178604742;178604741	chr2:179469470;179469469;179469468
Novex-2	9243	27952;27953;27954	chr2:178604743;178604742;178604741	chr2:179469470;179469469;179469468
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: Fn3-19
• Domain position: 52
• Structural Position: 67
• Q(SASA): 0.4569
• 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/D	rs773746281	-0.804	0.978	N	0.46	0.199	0.303781844768	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	1.2955E-04	0	None	0	0	None	0	None	0	8.89E-06	1.66113E-04
E/D	rs773746281	-0.804	0.978	N	0.46	0.199	0.303781844768	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	1.20709E-04	0	0	0	0	None	0	0	0	0	0
E/D	rs773746281	-0.804	0.978	N	0.46	0.199	0.303781844768	gnomAD-4.0.0	7.4456E-06	None	None	None	None	N	None	9.35804E-05	0	None	0	0	None	0	0	3.39364E-06	0	1.60411E-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	0.1561	likely_benign	0.16	benign	-0.662	Destabilizing	0.978	D	0.513	neutral	N	0.445314769	None	None	N
E/C	0.8181	likely_pathogenic	0.8402	pathogenic	-0.19	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/D	0.2829	likely_benign	0.2978	benign	-0.805	Destabilizing	0.978	D	0.46	neutral	N	0.454646328	None	None	N
E/F	0.8001	likely_pathogenic	0.8227	pathogenic	-0.555	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
E/G	0.2856	likely_benign	0.3294	benign	-0.922	Destabilizing	0.997	D	0.623	neutral	N	0.476715111	None	None	N
E/H	0.6744	likely_pathogenic	0.691	pathogenic	-0.661	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
E/I	0.278	likely_benign	0.2881	benign	0.013	Stabilizing	0.99	D	0.667	neutral	None	None	None	None	N
E/K	0.2476	likely_benign	0.2656	benign	-0.19	Destabilizing	0.956	D	0.473	neutral	N	0.420629755	None	None	N
E/L	0.3471	ambiguous	0.3697	ambiguous	0.013	Stabilizing	0.967	D	0.621	neutral	None	None	None	None	N
E/M	0.3719	ambiguous	0.3906	ambiguous	0.346	Stabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
E/N	0.3576	ambiguous	0.3889	ambiguous	-0.48	Destabilizing	0.998	D	0.596	neutral	None	None	None	None	N
E/P	0.4037	ambiguous	0.4214	ambiguous	-0.191	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
E/Q	0.1816	likely_benign	0.1904	benign	-0.443	Destabilizing	0.798	D	0.339	neutral	N	0.41022076	None	None	N
E/R	0.4011	ambiguous	0.4189	ambiguous	-0.004	Destabilizing	0.995	D	0.587	neutral	None	None	None	None	N
E/S	0.3067	likely_benign	0.3387	benign	-0.695	Destabilizing	0.983	D	0.529	neutral	None	None	None	None	N
E/T	0.229	likely_benign	0.2467	benign	-0.493	Destabilizing	0.983	D	0.625	neutral	None	None	None	None	N
E/V	0.1613	likely_benign	0.1589	benign	-0.191	Destabilizing	0.576	D	0.397	neutral	N	0.41964832	None	None	N
E/W	0.948	likely_pathogenic	0.9472	pathogenic	-0.407	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/Y	0.743	likely_pathogenic	0.7607	pathogenic	-0.327	Destabilizing	0.999	D	0.738	prob.delet.	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.