TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30544	91855;91856;91857	chr2:178550208;178550207;178550206	chr2:179414935;179414934;179414933
N2AB	28903	86932;86933;86934	chr2:178550208;178550207;178550206	chr2:179414935;179414934;179414933
N2A	27976	84151;84152;84153	chr2:178550208;178550207;178550206	chr2:179414935;179414934;179414933
N2B	21479	64660;64661;64662	chr2:178550208;178550207;178550206	chr2:179414935;179414934;179414933
Novex-1	21604	65035;65036;65037	chr2:178550208;178550207;178550206	chr2:179414935;179414934;179414933
Novex-2	21671	65236;65237;65238	chr2:178550208;178550207;178550206	chr2:179414935;179414934;179414933
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-149
• Domain position: 13
• Structural Position: 28
• Q(SASA): 0.2293
• 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/F	rs775973411	-1.455	0.934	N	0.661	0.152	0.37479162749	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/F	rs775973411	-1.455	0.934	N	0.661	0.152	0.37479162749	gnomAD-4.0.0	1.59158E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	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	0.7272	likely_pathogenic	0.7394	pathogenic	-2.446	Highly Destabilizing	0.688	D	0.553	neutral	None	None	None	None	N
L/C	0.684	likely_pathogenic	0.68	pathogenic	-1.689	Destabilizing	0.998	D	0.655	neutral	None	None	None	None	N
L/D	0.9955	likely_pathogenic	0.995	pathogenic	-2.66	Highly Destabilizing	0.991	D	0.729	prob.delet.	None	None	None	None	N
L/E	0.9729	likely_pathogenic	0.9699	pathogenic	-2.382	Highly Destabilizing	0.991	D	0.719	prob.delet.	None	None	None	None	N
L/F	0.2053	likely_benign	0.221	benign	-1.451	Destabilizing	0.934	D	0.661	neutral	N	0.480722916	None	None	N
L/G	0.9493	likely_pathogenic	0.9484	pathogenic	-3.016	Highly Destabilizing	0.991	D	0.716	prob.delet.	None	None	None	None	N
L/H	0.9042	likely_pathogenic	0.896	pathogenic	-2.408	Highly Destabilizing	0.997	D	0.673	neutral	N	0.479498043	None	None	N
L/I	0.1047	likely_benign	0.1062	benign	-0.774	Destabilizing	0.002	N	0.171	neutral	N	0.38579117	None	None	N
L/K	0.9591	likely_pathogenic	0.9531	pathogenic	-1.947	Destabilizing	0.974	D	0.697	prob.neutral	None	None	None	None	N
L/M	0.1522	likely_benign	0.1538	benign	-0.732	Destabilizing	0.949	D	0.635	neutral	None	None	None	None	N
L/N	0.969	likely_pathogenic	0.9645	pathogenic	-2.449	Highly Destabilizing	0.991	D	0.72	prob.delet.	None	None	None	None	N
L/P	0.9768	likely_pathogenic	0.974	pathogenic	-1.316	Destabilizing	0.989	D	0.727	prob.delet.	N	0.479498043	None	None	N
L/Q	0.876	likely_pathogenic	0.8626	pathogenic	-2.194	Highly Destabilizing	0.991	D	0.663	neutral	None	None	None	None	N
L/R	0.9261	likely_pathogenic	0.9182	pathogenic	-1.853	Destabilizing	0.989	D	0.689	prob.neutral	N	0.479244553	None	None	N
L/S	0.9139	likely_pathogenic	0.9132	pathogenic	-3.146	Highly Destabilizing	0.915	D	0.696	prob.neutral	None	None	None	None	N
L/T	0.7659	likely_pathogenic	0.7703	pathogenic	-2.7	Highly Destabilizing	0.842	D	0.62	neutral	None	None	None	None	N
L/V	0.1175	likely_benign	0.1244	benign	-1.316	Destabilizing	0.022	N	0.193	neutral	N	0.391847564	None	None	N
L/W	0.7721	likely_pathogenic	0.7804	pathogenic	-1.773	Destabilizing	0.998	D	0.638	neutral	None	None	None	None	N
L/Y	0.7944	likely_pathogenic	0.7879	pathogenic	-1.486	Destabilizing	0.991	D	0.725	prob.delet.	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.