TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8000	24223;24224;24225	chr2:178719392;178719391;178719390	chr2:179584119;179584118;179584117
N2AB	7683	23272;23273;23274	chr2:178719392;178719391;178719390	chr2:179584119;179584118;179584117
N2A	6756	20491;20492;20493	chr2:178719392;178719391;178719390	chr2:179584119;179584118;179584117
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-65
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.2083
• Predicted PPI site: I

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
A/P	None	None	0.106	N	0.464	0.032	0.112648838833	gnomAD-4.0.0	6.84253E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99531E-07	0	0
A/S	rs2077990712	None	None	N	0.099	0.049	0.0401082797425	gnomAD-4.0.0	6.84253E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99531E-07	0	0
A/T	None	None	None	N	0.15	0.025	0.0611884634855	gnomAD-4.0.0	4.78977E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.39719E-06	0	1.65656E-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
A/C	0.3078	likely_benign	0.3052	benign	-0.806	Destabilizing	0.676	D	0.4	neutral	None	None	None	None	I
A/D	0.1243	likely_benign	0.1251	benign	0.05	Stabilizing	0.012	N	0.404	neutral	N	0.364738321	None	None	I
A/E	0.136	likely_benign	0.1383	benign	-0.051	Destabilizing	0.001	N	0.175	neutral	None	None	None	None	I
A/F	0.2035	likely_benign	0.2077	benign	-0.724	Destabilizing	0.356	N	0.445	neutral	None	None	None	None	I
A/G	0.0813	likely_benign	0.0846	benign	-0.532	Destabilizing	None	N	0.145	neutral	N	0.409761321	None	None	I
A/H	0.2487	likely_benign	0.2652	benign	-0.553	Destabilizing	0.356	N	0.439	neutral	None	None	None	None	I
A/I	0.1704	likely_benign	0.1985	benign	-0.205	Destabilizing	0.038	N	0.481	neutral	None	None	None	None	I
A/K	0.1988	likely_benign	0.2103	benign	-0.62	Destabilizing	None	N	0.145	neutral	None	None	None	None	I
A/L	0.1272	likely_benign	0.1406	benign	-0.205	Destabilizing	0.016	N	0.43	neutral	None	None	None	None	I
A/M	0.147	likely_benign	0.1623	benign	-0.328	Destabilizing	0.356	N	0.423	neutral	None	None	None	None	I
A/N	0.1135	likely_benign	0.113	benign	-0.342	Destabilizing	0.038	N	0.393	neutral	None	None	None	None	I
A/P	0.2678	likely_benign	0.3345	benign	-0.229	Destabilizing	0.106	N	0.464	neutral	N	0.467521546	None	None	I
A/Q	0.1902	likely_benign	0.1933	benign	-0.515	Destabilizing	0.072	N	0.463	neutral	None	None	None	None	I
A/R	0.1964	likely_benign	0.2034	benign	-0.308	Destabilizing	0.038	N	0.447	neutral	None	None	None	None	I
A/S	0.0637	likely_benign	0.0597	benign	-0.711	Destabilizing	None	N	0.099	neutral	N	0.342536252	None	None	I
A/T	0.0607	likely_benign	0.0613	benign	-0.708	Destabilizing	None	N	0.15	neutral	N	0.405510295	None	None	I
A/V	0.0991	likely_benign	0.1098	benign	-0.229	Destabilizing	0.029	N	0.314	neutral	N	0.463654521	None	None	I
A/W	0.5033	ambiguous	0.5369	ambiguous	-0.918	Destabilizing	0.864	D	0.463	neutral	None	None	None	None	I
A/Y	0.2469	likely_benign	0.2635	benign	-0.537	Destabilizing	0.356	N	0.446	neutral	None	None	None	None	I

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.