TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9126	27601;27602;27603	chr2:178712546;178712545;178712544	chr2:179577273;179577272;179577271
N2AB	8809	26650;26651;26652	chr2:178712546;178712545;178712544	chr2:179577273;179577272;179577271
N2A	7882	23869;23870;23871	chr2:178712546;178712545;178712544	chr2:179577273;179577272;179577271
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-77
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.3313
• 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/R	None	None	1.0	D	0.851	0.758	0.877092428509	gnomAD-4.0.0	1.59228E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43324E-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
G/A	0.3138	likely_benign	0.3383	benign	-0.443	Destabilizing	1.0	D	0.779	deleterious	D	0.625915449	None	None	I
G/C	0.4804	ambiguous	0.5199	ambiguous	-0.953	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	I
G/D	0.1804	likely_benign	0.1946	benign	-0.458	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
G/E	0.191	likely_benign	0.2188	benign	-0.599	Destabilizing	1.0	D	0.835	deleterious	D	0.601054189	None	None	I
G/F	0.787	likely_pathogenic	0.8145	pathogenic	-1.044	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
G/H	0.55	ambiguous	0.5854	pathogenic	-0.706	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
G/I	0.7336	likely_pathogenic	0.7638	pathogenic	-0.454	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
G/K	0.5399	ambiguous	0.6017	pathogenic	-0.854	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/L	0.6657	likely_pathogenic	0.7063	pathogenic	-0.454	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
G/M	0.6794	likely_pathogenic	0.7194	pathogenic	-0.438	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
G/N	0.2702	likely_benign	0.2724	benign	-0.537	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/P	0.9773	likely_pathogenic	0.9739	pathogenic	-0.414	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
G/Q	0.364	ambiguous	0.4129	ambiguous	-0.803	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
G/R	0.4395	ambiguous	0.4963	ambiguous	-0.447	Destabilizing	1.0	D	0.851	deleterious	D	0.626117253	None	None	I
G/S	0.1699	likely_benign	0.1759	benign	-0.771	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
G/T	0.3902	ambiguous	0.4215	ambiguous	-0.832	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
G/V	0.569	likely_pathogenic	0.6101	pathogenic	-0.414	Destabilizing	1.0	D	0.823	deleterious	D	0.658589944	None	None	I
G/W	0.6	likely_pathogenic	0.6324	pathogenic	-1.208	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
G/Y	0.6042	likely_pathogenic	0.6391	pathogenic	-0.849	Destabilizing	1.0	D	0.827	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.