TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21627	65104;65105;65106	chr2:178584762;178584761;178584760	chr2:179449489;179449488;179449487
N2AB	19986	60181;60182;60183	chr2:178584762;178584761;178584760	chr2:179449489;179449488;179449487
N2A	19059	57400;57401;57402	chr2:178584762;178584761;178584760	chr2:179449489;179449488;179449487
N2B	12562	37909;37910;37911	chr2:178584762;178584761;178584760	chr2:179449489;179449488;179449487
Novex-1	12687	38284;38285;38286	chr2:178584762;178584761;178584760	chr2:179449489;179449488;179449487
Novex-2	12754	38485;38486;38487	chr2:178584762;178584761;178584760	chr2:179449489;179449488;179449487
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-44
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.6029
• 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
G/V	rs2154180072	None	0.988	N	0.824	0.435	0.645059290664	gnomAD-4.0.0	2.05299E-06	None	None	None	None	I	None	8.96968E-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
G/A	0.4407	ambiguous	0.4709	ambiguous	-0.538	Destabilizing	0.919	D	0.607	neutral	N	0.49810491	None	None	I
G/C	0.4744	ambiguous	0.488	ambiguous	-0.905	Destabilizing	0.999	D	0.831	deleterious	D	0.536341336	None	None	I
G/D	0.3327	likely_benign	0.3735	ambiguous	-1.111	Destabilizing	0.976	D	0.743	deleterious	D	0.524239699	None	None	I
G/E	0.3897	ambiguous	0.4397	ambiguous	-1.251	Destabilizing	0.991	D	0.821	deleterious	None	None	None	None	I
G/F	0.8132	likely_pathogenic	0.8363	pathogenic	-1.112	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	I
G/H	0.4623	ambiguous	0.5407	ambiguous	-0.94	Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	I
G/I	0.877	likely_pathogenic	0.9073	pathogenic	-0.506	Destabilizing	0.995	D	0.843	deleterious	None	None	None	None	I
G/K	0.4902	ambiguous	0.5857	pathogenic	-1.263	Destabilizing	0.991	D	0.817	deleterious	None	None	None	None	I
G/L	0.7562	likely_pathogenic	0.7647	pathogenic	-0.506	Destabilizing	0.991	D	0.82	deleterious	None	None	None	None	I
G/M	0.7847	likely_pathogenic	0.8001	pathogenic	-0.445	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/N	0.3374	likely_benign	0.3425	ambiguous	-0.834	Destabilizing	0.484	N	0.49	neutral	None	None	None	None	I
G/P	0.9864	likely_pathogenic	0.9901	pathogenic	-0.48	Destabilizing	0.995	D	0.849	deleterious	None	None	None	None	I
G/Q	0.3899	ambiguous	0.4448	ambiguous	-1.133	Destabilizing	0.991	D	0.85	deleterious	None	None	None	None	I
G/R	0.3779	ambiguous	0.4711	ambiguous	-0.754	Destabilizing	0.988	D	0.845	deleterious	D	0.523717583	None	None	I
G/S	0.224	likely_benign	0.2244	benign	-0.955	Destabilizing	0.414	N	0.476	neutral	N	0.497090952	None	None	I
G/T	0.526	ambiguous	0.5804	pathogenic	-1.036	Destabilizing	0.982	D	0.789	deleterious	None	None	None	None	I
G/V	0.7883	likely_pathogenic	0.8312	pathogenic	-0.48	Destabilizing	0.988	D	0.824	deleterious	N	0.521844706	None	None	I
G/W	0.6686	likely_pathogenic	0.739	pathogenic	-1.325	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/Y	0.6531	likely_pathogenic	0.6965	pathogenic	-0.987	Destabilizing	1.0	D	0.841	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.