TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32467	97624;97625;97626	chr2:178542357;178542356;178542355	chr2:179407084;179407083;179407082
N2AB	30826	92701;92702;92703	chr2:178542357;178542356;178542355	chr2:179407084;179407083;179407082
N2A	29899	89920;89921;89922	chr2:178542357;178542356;178542355	chr2:179407084;179407083;179407082
N2B	23402	70429;70430;70431	chr2:178542357;178542356;178542355	chr2:179407084;179407083;179407082
Novex-1	23527	70804;70805;70806	chr2:178542357;178542356;178542355	chr2:179407084;179407083;179407082
Novex-2	23594	71005;71006;71007	chr2:178542357;178542356;178542355	chr2:179407084;179407083;179407082
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: Fn3-124
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.5854
• 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/E	rs2154142486	None	1.0	N	0.855	0.572	0.665958451526	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
G/R	rs2154142487	None	1.0	D	0.842	0.567	0.765156682138	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.4479	ambiguous	0.3072	benign	-0.533	Destabilizing	1.0	D	0.693	prob.neutral	N	0.511107057	None	None	N
G/C	0.5377	ambiguous	0.3705	ambiguous	-0.826	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/D	0.2964	likely_benign	0.24	benign	-1.18	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/E	0.4135	ambiguous	0.3189	benign	-1.345	Destabilizing	1.0	D	0.855	deleterious	N	0.513740403	None	None	N
G/F	0.8628	likely_pathogenic	0.7425	pathogenic	-1.241	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
G/H	0.635	likely_pathogenic	0.5069	ambiguous	-0.82	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
G/I	0.8832	likely_pathogenic	0.7662	pathogenic	-0.588	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
G/K	0.6358	likely_pathogenic	0.5505	ambiguous	-1.083	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/L	0.8274	likely_pathogenic	0.6869	pathogenic	-0.588	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
G/M	0.8149	likely_pathogenic	0.6705	pathogenic	-0.378	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
G/N	0.3105	likely_benign	0.2393	benign	-0.651	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
G/P	0.9891	likely_pathogenic	0.977	pathogenic	-0.535	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
G/Q	0.5452	ambiguous	0.4481	ambiguous	-1.02	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
G/R	0.5798	likely_pathogenic	0.5081	ambiguous	-0.521	Destabilizing	1.0	D	0.842	deleterious	D	0.537213482	None	None	N
G/S	0.2424	likely_benign	0.1643	benign	-0.755	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
G/T	0.5171	ambiguous	0.3657	ambiguous	-0.868	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
G/V	0.7978	likely_pathogenic	0.6477	pathogenic	-0.535	Destabilizing	1.0	D	0.846	deleterious	D	0.5447219	None	None	N
G/W	0.7304	likely_pathogenic	0.5568	ambiguous	-1.391	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/Y	0.7134	likely_pathogenic	0.5404	ambiguous	-1.064	Destabilizing	1.0	D	0.811	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.