TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29485	88678;88679;88680	chr2:178555006;178555005;178555004	chr2:179419733;179419732;179419731
N2AB	27844	83755;83756;83757	chr2:178555006;178555005;178555004	chr2:179419733;179419732;179419731
N2A	26917	80974;80975;80976	chr2:178555006;178555005;178555004	chr2:179419733;179419732;179419731
N2B	20420	61483;61484;61485	chr2:178555006;178555005;178555004	chr2:179419733;179419732;179419731
Novex-1	20545	61858;61859;61860	chr2:178555006;178555005;178555004	chr2:179419733;179419732;179419731
Novex-2	20612	62059;62060;62061	chr2:178555006;178555005;178555004	chr2:179419733;179419732;179419731
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-146
• Domain position: 42
• Structural Position: 102
• Q(SASA): 0.5175
• 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
A/V	None	None	0.211	N	0.224	0.157	0.275215494804	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	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
A/C	0.5684	likely_pathogenic	0.5139	ambiguous	-0.769	Destabilizing	0.999	D	0.324	neutral	None	None	None	None	N
A/D	0.3423	ambiguous	0.2713	benign	-0.672	Destabilizing	0.976	D	0.463	neutral	None	None	None	None	N
A/E	0.3509	ambiguous	0.2812	benign	-0.824	Destabilizing	0.968	D	0.344	neutral	N	0.368914776	None	None	N
A/F	0.4535	ambiguous	0.3751	ambiguous	-0.874	Destabilizing	0.988	D	0.502	neutral	None	None	None	None	N
A/G	0.1587	likely_benign	0.1412	benign	-0.23	Destabilizing	0.811	D	0.305	neutral	N	0.400005687	None	None	N
A/H	0.511	ambiguous	0.4481	ambiguous	-0.226	Destabilizing	0.999	D	0.517	neutral	None	None	None	None	N
A/I	0.3117	likely_benign	0.257	benign	-0.335	Destabilizing	0.851	D	0.342	neutral	None	None	None	None	N
A/K	0.5182	ambiguous	0.4371	ambiguous	-0.646	Destabilizing	0.976	D	0.33	neutral	None	None	None	None	N
A/L	0.22	likely_benign	0.191	benign	-0.335	Destabilizing	0.851	D	0.323	neutral	None	None	None	None	N
A/M	0.2832	likely_benign	0.2428	benign	-0.492	Destabilizing	0.997	D	0.354	neutral	None	None	None	None	N
A/N	0.2674	likely_benign	0.242	benign	-0.309	Destabilizing	0.976	D	0.503	neutral	None	None	None	None	N
A/P	0.1844	likely_benign	0.1508	benign	-0.263	Destabilizing	0.984	D	0.349	neutral	N	0.423037263	None	None	N
A/Q	0.398	ambiguous	0.3466	ambiguous	-0.59	Destabilizing	0.988	D	0.333	neutral	None	None	None	None	N
A/R	0.4696	ambiguous	0.3978	ambiguous	-0.16	Destabilizing	0.976	D	0.339	neutral	None	None	None	None	N
A/S	0.0959	likely_benign	0.0943	benign	-0.464	Destabilizing	0.103	N	0.231	neutral	N	0.430155236	None	None	N
A/T	0.1035	likely_benign	0.0938	benign	-0.544	Destabilizing	0.103	N	0.252	neutral	N	0.45047458	None	None	N
A/V	0.1628	likely_benign	0.1366	benign	-0.263	Destabilizing	0.211	N	0.224	neutral	N	0.443799324	None	None	N
A/W	0.8206	likely_pathogenic	0.7548	pathogenic	-1.003	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
A/Y	0.5338	ambiguous	0.4647	ambiguous	-0.672	Destabilizing	0.996	D	0.5	neutral	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.