TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5182	15769;15770;15771	chr2:178733845;178733844;178733843	chr2:179598572;179598571;179598570
N2AB	4865	14818;14819;14820	chr2:178733845;178733844;178733843	chr2:179598572;179598571;179598570
N2A	3938	12037;12038;12039	chr2:178733845;178733844;178733843	chr2:179598572;179598571;179598570
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-35
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.3375
• 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	rs775552018	-0.439	1.0	D	0.863	0.741	0.906498380218	gnomAD-2.1.1	2.43E-05	None	None	None	None	I	None	0	0	None	0	3.35196E-04	None	0	None	0	0	0
G/R	rs775552018	-0.439	1.0	D	0.863	0.741	0.906498380218	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/R	rs775552018	-0.439	1.0	D	0.863	0.741	0.906498380218	gnomAD-4.0.0	6.86816E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.0283E-07	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	0.2487	likely_benign	0.292	benign	-0.305	Destabilizing	1.0	D	0.784	deleterious	D	0.728926006	None	None	I
G/C	0.3807	ambiguous	0.4442	ambiguous	-0.873	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
G/D	0.1863	likely_benign	0.2305	benign	-0.592	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
G/E	0.2312	likely_benign	0.2877	benign	-0.761	Destabilizing	1.0	D	0.846	deleterious	D	0.726575865	None	None	I
G/F	0.6512	likely_pathogenic	0.7173	pathogenic	-1.089	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/H	0.3833	ambiguous	0.459	ambiguous	-0.545	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
G/I	0.5436	ambiguous	0.6027	pathogenic	-0.472	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/K	0.338	likely_benign	0.4182	ambiguous	-0.724	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
G/L	0.557	ambiguous	0.634	pathogenic	-0.472	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/M	0.6053	likely_pathogenic	0.6684	pathogenic	-0.401	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
G/N	0.2217	likely_benign	0.2753	benign	-0.409	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
G/P	0.8989	likely_pathogenic	0.9255	pathogenic	-0.384	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
G/Q	0.2889	likely_benign	0.3604	ambiguous	-0.726	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/R	0.2494	likely_benign	0.3041	benign	-0.279	Destabilizing	1.0	D	0.863	deleterious	D	0.765550372	None	None	I
G/S	0.115	likely_benign	0.1334	benign	-0.553	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
G/T	0.2939	likely_benign	0.3377	benign	-0.655	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	I
G/V	0.4339	ambiguous	0.4942	ambiguous	-0.384	Destabilizing	1.0	D	0.83	deleterious	D	0.851062377	None	None	I
G/W	0.5068	ambiguous	0.5757	pathogenic	-1.219	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
G/Y	0.4997	ambiguous	0.5915	pathogenic	-0.866	Destabilizing	1.0	D	0.84	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.