TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21266	64021;64022;64023	chr2:178587415;178587414;178587413	chr2:179452142;179452141;179452140
N2AB	19625	59098;59099;59100	chr2:178587415;178587414;178587413	chr2:179452142;179452141;179452140
N2A	18698	56317;56318;56319	chr2:178587415;178587414;178587413	chr2:179452142;179452141;179452140
N2B	12201	36826;36827;36828	chr2:178587415;178587414;178587413	chr2:179452142;179452141;179452140
Novex-1	12326	37201;37202;37203	chr2:178587415;178587414;178587413	chr2:179452142;179452141;179452140
Novex-2	12393	37402;37403;37404	chr2:178587415;178587414;178587413	chr2:179452142;179452141;179452140
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-42
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.3255
• 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
T/A	rs1453662624	None	0.997	N	0.488	0.221	0.137902524267	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
T/A	rs1453662624	None	0.997	N	0.488	0.221	0.137902524267	gnomAD-4.0.0	2.03051E-06	None	None	None	None	I	None	1.74948E-05	0	None	0	0	None	0	0	1.20504E-06	0	0
T/I	None	None	0.999	N	0.669	0.302	0.280987212366	gnomAD-4.0.0	2.061E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.70524E-06	0	0
T/S	None	None	0.997	N	0.567	0.137	0.132336055621	gnomAD-4.0.0	6.87001E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.01746E-07	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
T/A	0.1923	likely_benign	0.1899	benign	-0.813	Destabilizing	0.997	D	0.488	neutral	N	0.474772805	None	None	I
T/C	0.6346	likely_pathogenic	0.6515	pathogenic	-0.477	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	I
T/D	0.9116	likely_pathogenic	0.9073	pathogenic	-0.167	Destabilizing	0.999	D	0.686	prob.delet.	None	None	None	None	I
T/E	0.8129	likely_pathogenic	0.7927	pathogenic	-0.218	Destabilizing	0.999	D	0.687	prob.delet.	None	None	None	None	I
T/F	0.7488	likely_pathogenic	0.7345	pathogenic	-1.206	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	I
T/G	0.5661	likely_pathogenic	0.5856	pathogenic	-0.979	Destabilizing	0.999	D	0.671	prob.neutral	None	None	None	None	I
T/H	0.6824	likely_pathogenic	0.665	pathogenic	-1.356	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
T/I	0.4737	ambiguous	0.4523	ambiguous	-0.476	Destabilizing	0.999	D	0.669	prob.neutral	N	0.483259002	None	None	I
T/K	0.6045	likely_pathogenic	0.5303	ambiguous	-0.555	Destabilizing	0.999	D	0.692	prob.delet.	None	None	None	None	I
T/L	0.3088	likely_benign	0.2967	benign	-0.476	Destabilizing	0.998	D	0.694	prob.delet.	None	None	None	None	I
T/M	0.2044	likely_benign	0.2024	benign	-0.011	Destabilizing	1.0	D	0.597	neutral	None	None	None	None	I
T/N	0.4166	ambiguous	0.4289	ambiguous	-0.393	Destabilizing	0.999	D	0.675	prob.neutral	N	0.456248319	None	None	I
T/P	0.3861	ambiguous	0.348	ambiguous	-0.56	Destabilizing	0.999	D	0.639	neutral	N	0.450970439	None	None	I
T/Q	0.5988	likely_pathogenic	0.57	pathogenic	-0.714	Destabilizing	0.999	D	0.667	prob.neutral	None	None	None	None	I
T/R	0.5839	likely_pathogenic	0.5	ambiguous	-0.254	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	I
T/S	0.1665	likely_benign	0.1874	benign	-0.672	Destabilizing	0.997	D	0.567	neutral	N	0.479834695	None	None	I
T/V	0.2966	likely_benign	0.2827	benign	-0.56	Destabilizing	0.998	D	0.654	prob.neutral	None	None	None	None	I
T/W	0.9535	likely_pathogenic	0.9515	pathogenic	-1.093	Destabilizing	1.0	D	0.728	deleterious	None	None	None	None	I
T/Y	0.7439	likely_pathogenic	0.7399	pathogenic	-0.852	Destabilizing	1.0	D	0.769	deleterious	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.