TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1487	4684;4685;4686	chr2:178777725;178777724;178777723	chr2:179642452;179642451;179642450
N2AB	1487	4684;4685;4686	chr2:178777725;178777724;178777723	chr2:179642452;179642451;179642450
N2A	1487	4684;4685;4686	chr2:178777725;178777724;178777723	chr2:179642452;179642451;179642450
N2B	1441	4546;4547;4548	chr2:178777725;178777724;178777723	chr2:179642452;179642451;179642450
Novex-1	1441	4546;4547;4548	chr2:178777725;178777724;178777723	chr2:179642452;179642451;179642450
Novex-2	1441	4546;4547;4548	chr2:178777725;178777724;178777723	chr2:179642452;179642451;179642450
Novex-3	1487	4684;4685;4686	chr2:178777725;178777724;178777723	chr2:179642452;179642451;179642450

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-6
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.7541
• 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
E/D	None	None	None	N	0.186	0.096	0.0954503805726	gnomAD-4.0.0	6.84115E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15939E-05	0
E/G	rs1561308394	None	0.324	D	0.543	0.495	0.518858945281	gnomAD-2.1.1	3.99E-06	None	None	None	None	I	None	0	0	None	0	5.45E-05	None	0	None	0	0	0
E/G	rs1561308394	None	0.324	D	0.543	0.495	0.518858945281	gnomAD-4.0.0	1.59073E-06	None	None	None	None	I	None	0	0	None	0	2.77331E-05	None	0	0	0	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	0.4863	ambiguous	0.5009	ambiguous	-0.679	Destabilizing	0.09	N	0.474	neutral	N	0.513334978	None	None	I
E/C	0.9889	likely_pathogenic	0.9898	pathogenic	-0.382	Destabilizing	0.944	D	0.586	neutral	None	None	None	None	I
E/D	0.2266	likely_benign	0.2388	benign	-0.641	Destabilizing	None	N	0.186	neutral	N	0.450978089	None	None	I
E/F	0.9787	likely_pathogenic	0.9812	pathogenic	-0.218	Destabilizing	0.69	D	0.586	neutral	None	None	None	None	I
E/G	0.6071	likely_pathogenic	0.6109	pathogenic	-0.957	Destabilizing	0.324	N	0.543	neutral	D	0.611257358	None	None	I
E/H	0.8675	likely_pathogenic	0.8744	pathogenic	-0.126	Destabilizing	0.932	D	0.456	neutral	None	None	None	None	I
E/I	0.8284	likely_pathogenic	0.8392	pathogenic	0.053	Stabilizing	0.098	N	0.574	neutral	None	None	None	None	I
E/K	0.483	ambiguous	0.4961	ambiguous	-0.161	Destabilizing	0.324	N	0.47	neutral	N	0.486443687	None	None	I
E/L	0.8491	likely_pathogenic	0.8552	pathogenic	0.053	Stabilizing	0.241	N	0.563	neutral	None	None	None	None	I
E/M	0.8737	likely_pathogenic	0.8769	pathogenic	0.189	Stabilizing	0.893	D	0.56	neutral	None	None	None	None	I
E/N	0.5783	likely_pathogenic	0.6056	pathogenic	-0.624	Destabilizing	0.388	N	0.467	neutral	None	None	None	None	I
E/P	0.9808	likely_pathogenic	0.9796	pathogenic	-0.171	Destabilizing	0.932	D	0.534	neutral	None	None	None	None	I
E/Q	0.3401	ambiguous	0.3513	ambiguous	-0.531	Destabilizing	0.492	N	0.503	neutral	N	0.49571653	None	None	I
E/R	0.6723	likely_pathogenic	0.6892	pathogenic	0.183	Stabilizing	0.818	D	0.483	neutral	None	None	None	None	I
E/S	0.5002	ambiguous	0.5181	ambiguous	-0.82	Destabilizing	0.388	N	0.444	neutral	None	None	None	None	I
E/T	0.6081	likely_pathogenic	0.6272	pathogenic	-0.59	Destabilizing	0.388	N	0.488	neutral	None	None	None	None	I
E/V	0.6071	likely_pathogenic	0.6235	pathogenic	-0.171	Destabilizing	0.001	N	0.4	neutral	N	0.513021411	None	None	I
E/W	0.9948	likely_pathogenic	0.9953	pathogenic	0.045	Stabilizing	0.981	D	0.632	neutral	None	None	None	None	I
E/Y	0.9525	likely_pathogenic	0.9562	pathogenic	0.036	Stabilizing	0.818	D	0.581	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.