TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8118	24577;24578;24579	chr2:178718848;178718847;178718846	chr2:179583575;179583574;179583573
N2AB	7801	23626;23627;23628	chr2:178718848;178718847;178718846	chr2:179583575;179583574;179583573
N2A	6874	20845;20846;20847	chr2:178718848;178718847;178718846	chr2:179583575;179583574;179583573
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: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-66
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.2452
• 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
L/P	rs780410071	-1.247	0.99	D	0.835	0.598	0.902064092376	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.56E-05	0
L/P	rs780410071	-1.247	0.99	D	0.835	0.598	0.902064092376	gnomAD-4.0.0	8.21065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.07938E-05	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
L/A	0.5126	ambiguous	0.5569	ambiguous	-2.166	Highly Destabilizing	0.754	D	0.509	neutral	None	None	None	None	N
L/C	0.7845	likely_pathogenic	0.8019	pathogenic	-1.228	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	N
L/D	0.9604	likely_pathogenic	0.9684	pathogenic	-2.532	Highly Destabilizing	0.978	D	0.835	deleterious	None	None	None	None	N
L/E	0.771	likely_pathogenic	0.7975	pathogenic	-2.293	Highly Destabilizing	0.978	D	0.819	deleterious	None	None	None	None	N
L/F	0.2758	likely_benign	0.2843	benign	-1.325	Destabilizing	0.956	D	0.668	neutral	None	None	None	None	N
L/G	0.8801	likely_pathogenic	0.9035	pathogenic	-2.681	Highly Destabilizing	0.978	D	0.813	deleterious	None	None	None	None	N
L/H	0.6323	likely_pathogenic	0.6634	pathogenic	-2.057	Highly Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
L/I	0.0864	likely_benign	0.0854	benign	-0.676	Destabilizing	0.16	N	0.341	neutral	None	None	None	None	N
L/K	0.6188	likely_pathogenic	0.6457	pathogenic	-1.609	Destabilizing	0.956	D	0.781	deleterious	None	None	None	None	N
L/M	0.1476	likely_benign	0.1462	benign	-0.534	Destabilizing	0.247	N	0.425	neutral	N	0.502340051	None	None	N
L/N	0.8554	likely_pathogenic	0.8728	pathogenic	-2.032	Highly Destabilizing	0.978	D	0.837	deleterious	None	None	None	None	N
L/P	0.9199	likely_pathogenic	0.9369	pathogenic	-1.155	Destabilizing	0.99	D	0.835	deleterious	D	0.544170875	None	None	N
L/Q	0.491	ambiguous	0.5235	ambiguous	-1.88	Destabilizing	0.971	D	0.815	deleterious	D	0.55100773	None	None	N
L/R	0.4732	ambiguous	0.5091	ambiguous	-1.405	Destabilizing	0.942	D	0.809	deleterious	D	0.55075424	None	None	N
L/S	0.791	likely_pathogenic	0.8295	pathogenic	-2.661	Highly Destabilizing	0.956	D	0.757	deleterious	None	None	None	None	N
L/T	0.5113	ambiguous	0.5707	pathogenic	-2.274	Highly Destabilizing	0.956	D	0.679	prob.neutral	None	None	None	None	N
L/V	0.1068	likely_benign	0.1097	benign	-1.155	Destabilizing	0.489	N	0.471	neutral	N	0.496980772	None	None	N
L/W	0.4812	ambiguous	0.5079	ambiguous	-1.695	Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	N
L/Y	0.6138	likely_pathogenic	0.6285	pathogenic	-1.335	Destabilizing	0.978	D	0.769	deleterious	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.