TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32401	97426;97427;97428	chr2:178542555;178542554;178542553	chr2:179407282;179407281;179407280
N2AB	30760	92503;92504;92505	chr2:178542555;178542554;178542553	chr2:179407282;179407281;179407280
N2A	29833	89722;89723;89724	chr2:178542555;178542554;178542553	chr2:179407282;179407281;179407280
N2B	23336	70231;70232;70233	chr2:178542555;178542554;178542553	chr2:179407282;179407281;179407280
Novex-1	23461	70606;70607;70608	chr2:178542555;178542554;178542553	chr2:179407282;179407281;179407280
Novex-2	23528	70807;70808;70809	chr2:178542555;178542554;178542553	chr2:179407282;179407281;179407280
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-124
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.229
• 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	rs1371025709	-0.866	0.999	N	0.859	0.437	0.499218193508	gnomAD-2.1.1	1.23E-05	None	None	None	None	N	None	6.48E-05	5.86E-05	None	0	0	None	0	None	0	0	0
G/R	rs1371025709	-0.866	0.999	N	0.859	0.437	0.499218193508	gnomAD-4.0.0	2.76105E-06	None	None	None	None	N	None	3.01823E-05	4.52489E-05	None	0	0	None	0	0	9.0688E-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	0.2459	likely_benign	0.227	benign	-0.875	Destabilizing	0.884	D	0.369	neutral	N	0.498737479	None	None	N
G/C	0.5307	ambiguous	0.4591	ambiguous	-1.256	Destabilizing	1.0	D	0.864	deleterious	N	0.512121701	None	None	N
G/D	0.6318	likely_pathogenic	0.5848	pathogenic	-2.066	Highly Destabilizing	0.64	D	0.41	neutral	N	0.480949416	None	None	N
G/E	0.6774	likely_pathogenic	0.6115	pathogenic	-2.099	Highly Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	N
G/F	0.8703	likely_pathogenic	0.8377	pathogenic	-1.203	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/H	0.8518	likely_pathogenic	0.8103	pathogenic	-1.375	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/I	0.7836	likely_pathogenic	0.7184	pathogenic	-0.478	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
G/K	0.8745	likely_pathogenic	0.8322	pathogenic	-1.293	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/L	0.6974	likely_pathogenic	0.6415	pathogenic	-0.478	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
G/M	0.788	likely_pathogenic	0.7396	pathogenic	-0.494	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
G/N	0.6593	likely_pathogenic	0.6248	pathogenic	-1.164	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	N
G/P	0.986	likely_pathogenic	0.9807	pathogenic	-0.572	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
G/Q	0.7403	likely_pathogenic	0.6896	pathogenic	-1.388	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
G/R	0.8153	likely_pathogenic	0.7547	pathogenic	-0.972	Destabilizing	0.999	D	0.859	deleterious	N	0.511107743	None	None	N
G/S	0.1758	likely_benign	0.1653	benign	-1.354	Destabilizing	0.992	D	0.555	neutral	N	0.499764463	None	None	N
G/T	0.4466	ambiguous	0.4122	ambiguous	-1.324	Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	N
G/V	0.6675	likely_pathogenic	0.5939	pathogenic	-0.572	Destabilizing	0.999	D	0.831	deleterious	N	0.511614722	None	None	N
G/W	0.8545	likely_pathogenic	0.8132	pathogenic	-1.569	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
G/Y	0.8293	likely_pathogenic	0.7829	pathogenic	-1.153	Destabilizing	1.0	D	0.866	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.