TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35716	107371;107372;107373	chr2:178528605;178528604;178528603	chr2:179393332;179393331;179393330
N2AB	34075	102448;102449;102450	chr2:178528605;178528604;178528603	chr2:179393332;179393331;179393330
N2A	33148	99667;99668;99669	chr2:178528605;178528604;178528603	chr2:179393332;179393331;179393330
N2B	26651	80176;80177;80178	chr2:178528605;178528604;178528603	chr2:179393332;179393331;179393330
Novex-1	26776	80551;80552;80553	chr2:178528605;178528604;178528603	chr2:179393332;179393331;179393330
Novex-2	26843	80752;80753;80754	chr2:178528605;178528604;178528603	chr2:179393332;179393331;179393330
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-168
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.3109
• 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
G/R	None	None	1.0	D	0.898	0.875	0.896683022151	gnomAD-4.0.0	1.59418E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86256E-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
G/A	0.5445	ambiguous	0.5605	ambiguous	-0.396	Destabilizing	1.0	D	0.777	deleterious	D	0.61546804	None	None	N
G/C	0.7147	likely_pathogenic	0.7488	pathogenic	-0.874	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
G/D	0.4985	ambiguous	0.4897	ambiguous	-0.864	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
G/E	0.522	ambiguous	0.5186	ambiguous	-1.034	Destabilizing	1.0	D	0.873	deleterious	D	0.589910286	None	None	N
G/F	0.9053	likely_pathogenic	0.9225	pathogenic	-1.192	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
G/H	0.7617	likely_pathogenic	0.7794	pathogenic	-0.646	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
G/I	0.912	likely_pathogenic	0.9154	pathogenic	-0.531	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
G/K	0.723	likely_pathogenic	0.6989	pathogenic	-0.844	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
G/L	0.8767	likely_pathogenic	0.8944	pathogenic	-0.531	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
G/M	0.8886	likely_pathogenic	0.9018	pathogenic	-0.383	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
G/N	0.4962	ambiguous	0.5055	ambiguous	-0.499	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
G/P	0.9951	likely_pathogenic	0.9949	pathogenic	-0.453	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
G/Q	0.6522	likely_pathogenic	0.6539	pathogenic	-0.85	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
G/R	0.6177	likely_pathogenic	0.6112	pathogenic	-0.347	Destabilizing	1.0	D	0.898	deleterious	D	0.615669844	None	None	N
G/S	0.2894	likely_benign	0.3007	benign	-0.623	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
G/T	0.6724	likely_pathogenic	0.6818	pathogenic	-0.733	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
G/V	0.8471	likely_pathogenic	0.8505	pathogenic	-0.453	Destabilizing	1.0	D	0.853	deleterious	D	0.632123174	None	None	N
G/W	0.8131	likely_pathogenic	0.8359	pathogenic	-1.32	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
G/Y	0.808	likely_pathogenic	0.8334	pathogenic	-0.971	Destabilizing	1.0	D	0.868	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.