TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20684	62275;62276;62277	chr2:178589675;178589674;178589673	chr2:179454402;179454401;179454400
N2AB	19043	57352;57353;57354	chr2:178589675;178589674;178589673	chr2:179454402;179454401;179454400
N2A	18116	54571;54572;54573	chr2:178589675;178589674;178589673	chr2:179454402;179454401;179454400
N2B	11619	35080;35081;35082	chr2:178589675;178589674;178589673	chr2:179454402;179454401;179454400
Novex-1	11744	35455;35456;35457	chr2:178589675;178589674;178589673	chr2:179454402;179454401;179454400
Novex-2	11811	35656;35657;35658	chr2:178589675;178589674;178589673	chr2:179454402;179454401;179454400
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-38
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.3018
• 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
F/V	rs2049802658	None	0.999	N	0.593	0.261	0.774620572007	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
F/V	rs2049802658	None	0.999	N	0.593	0.261	0.774620572007	gnomAD-4.0.0	6.57696E-06	None	None	None	None	I	None	2.41336E-05	0	None	0	0	None	0	0	0	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
F/A	0.9439	likely_pathogenic	0.8943	pathogenic	-2.581	Highly Destabilizing	0.993	D	0.629	neutral	None	None	None	None	I
F/C	0.8346	likely_pathogenic	0.7604	pathogenic	-1.246	Destabilizing	1.0	D	0.753	deleterious	N	0.471303717	None	None	I
F/D	0.9901	likely_pathogenic	0.9787	pathogenic	-1.847	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	I
F/E	0.9891	likely_pathogenic	0.9754	pathogenic	-1.786	Destabilizing	0.996	D	0.697	prob.neutral	None	None	None	None	I
F/G	0.9818	likely_pathogenic	0.9672	pathogenic	-2.91	Highly Destabilizing	0.998	D	0.684	prob.neutral	None	None	None	None	I
F/H	0.7817	likely_pathogenic	0.6646	pathogenic	-1.216	Destabilizing	0.171	N	0.305	neutral	None	None	None	None	I
F/I	0.9046	likely_pathogenic	0.8494	pathogenic	-1.576	Destabilizing	0.999	D	0.504	neutral	N	0.521673823	None	None	I
F/K	0.989	likely_pathogenic	0.9748	pathogenic	-1.253	Destabilizing	0.998	D	0.738	prob.delet.	None	None	None	None	I
F/L	0.9933	likely_pathogenic	0.9878	pathogenic	-1.576	Destabilizing	0.99	D	0.446	neutral	N	0.521500464	None	None	I
F/M	0.9001	likely_pathogenic	0.8463	pathogenic	-1.141	Destabilizing	1.0	D	0.519	neutral	None	None	None	None	I
F/N	0.9399	likely_pathogenic	0.8911	pathogenic	-1.206	Destabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	I
F/P	0.9999	likely_pathogenic	0.9998	pathogenic	-1.908	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	I
F/Q	0.9703	likely_pathogenic	0.9433	pathogenic	-1.422	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	I
F/R	0.9723	likely_pathogenic	0.9438	pathogenic	-0.453	Destabilizing	0.996	D	0.749	deleterious	None	None	None	None	I
F/S	0.8557	likely_pathogenic	0.7654	pathogenic	-1.967	Destabilizing	0.997	D	0.665	neutral	N	0.374190097	None	None	I
F/T	0.9029	likely_pathogenic	0.8189	pathogenic	-1.815	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	I
F/V	0.8452	likely_pathogenic	0.7621	pathogenic	-1.908	Destabilizing	0.999	D	0.593	neutral	N	0.491350916	None	None	I
F/W	0.681	likely_pathogenic	0.6133	pathogenic	-0.813	Destabilizing	1.0	D	0.526	neutral	None	None	None	None	I
F/Y	0.2749	likely_benign	0.2164	benign	-0.99	Destabilizing	0.98	D	0.497	neutral	N	0.442962323	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.