TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32422	97489;97490;97491	chr2:178542492;178542491;178542490	chr2:179407219;179407218;179407217
N2AB	30781	92566;92567;92568	chr2:178542492;178542491;178542490	chr2:179407219;179407218;179407217
N2A	29854	89785;89786;89787	chr2:178542492;178542491;178542490	chr2:179407219;179407218;179407217
N2B	23357	70294;70295;70296	chr2:178542492;178542491;178542490	chr2:179407219;179407218;179407217
Novex-1	23482	70669;70670;70671	chr2:178542492;178542491;178542490	chr2:179407219;179407218;179407217
Novex-2	23549	70870;70871;70872	chr2:178542492;178542491;178542490	chr2:179407219;179407218;179407217
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: Fn3-124
• Domain position: 24
• Structural Position: 25
• Q(SASA): 0.3833
• 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/K	rs1695041603	None	0.124	N	0.605	0.183	0.224531998449	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1695041603	None	0.124	N	0.605	0.183	0.224531998449	gnomAD-4.0.0	6.57488E-06	None	None	None	None	N	None	2.41464E-05	0	None	0	0	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	0.0995	likely_benign	0.1002	benign	-0.706	Destabilizing	0.124	N	0.666	neutral	N	0.469371003	None	None	N
E/C	0.6206	likely_pathogenic	0.5916	pathogenic	-0.285	Destabilizing	0.968	D	0.769	deleterious	None	None	None	None	N
E/D	0.0764	likely_benign	0.0763	benign	-0.804	Destabilizing	0.001	N	0.264	neutral	N	0.472247867	None	None	N
E/F	0.5508	ambiguous	0.4964	ambiguous	-0.265	Destabilizing	0.89	D	0.768	deleterious	None	None	None	None	N
E/G	0.0924	likely_benign	0.0929	benign	-1.02	Destabilizing	0.001	N	0.407	neutral	N	0.516636149	None	None	N
E/H	0.3126	likely_benign	0.2752	benign	-0.388	Destabilizing	0.726	D	0.621	neutral	None	None	None	None	N
E/I	0.2525	likely_benign	0.2244	benign	0.13	Stabilizing	0.726	D	0.774	deleterious	None	None	None	None	N
E/K	0.124	likely_benign	0.1084	benign	-0.221	Destabilizing	0.124	N	0.605	neutral	N	0.462857592	None	None	N
E/L	0.1862	likely_benign	0.1766	benign	0.13	Stabilizing	0.567	D	0.738	prob.delet.	None	None	None	None	N
E/M	0.2617	likely_benign	0.2455	benign	0.44	Stabilizing	0.909	D	0.771	deleterious	None	None	None	None	N
E/N	0.1123	likely_benign	0.1121	benign	-0.682	Destabilizing	0.272	N	0.615	neutral	None	None	None	None	N
E/P	0.6714	likely_pathogenic	0.6713	pathogenic	-0.127	Destabilizing	0.726	D	0.753	deleterious	None	None	None	None	N
E/Q	0.1032	likely_benign	0.0958	benign	-0.579	Destabilizing	0.009	N	0.259	neutral	N	0.466052613	None	None	N
E/R	0.2247	likely_benign	0.1945	benign	0.042	Stabilizing	0.396	N	0.625	neutral	None	None	None	None	N
E/S	0.1154	likely_benign	0.1149	benign	-0.914	Destabilizing	0.157	N	0.587	neutral	None	None	None	None	N
E/T	0.1568	likely_benign	0.1508	benign	-0.655	Destabilizing	0.567	D	0.721	prob.delet.	None	None	None	None	N
E/V	0.1661	likely_benign	0.1474	benign	-0.127	Destabilizing	0.497	N	0.741	deleterious	N	0.478525262	None	None	N
E/W	0.8224	likely_pathogenic	0.7696	pathogenic	-0.015	Destabilizing	0.968	D	0.761	deleterious	None	None	None	None	N
E/Y	0.4025	ambiguous	0.3519	ambiguous	-0.007	Destabilizing	0.89	D	0.786	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.