TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4639	14140;14141;14142	chr2:178739318;178739317;178739316	chr2:179604045;179604044;179604043
N2AB	4322	13189;13190;13191	chr2:178739318;178739317;178739316	chr2:179604045;179604044;179604043
N2A	None	None	chr2:None	chr2:None
N2B	4276	13051;13052;13053	chr2:178739318;178739317;178739316	chr2:179604045;179604044;179604043
Novex-1	4401	13426;13427;13428	chr2:178739318;178739317;178739316	chr2:179604045;179604044;179604043
Novex-2	4468	13627;13628;13629	chr2:178739318;178739317;178739316	chr2:179604045;179604044;179604043
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: Ig-29
• Domain position: 34
• Structural Position: 50
• Q(SASA): 0.1527
• 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
F/I	rs374885319	-0.911	0.379	N	0.551	0.233	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
F/I	rs374885319	-0.911	0.379	N	0.551	0.233	None	gnomAD-4.0.0	6.57099E-06	None	None	None	None	N	None	2.41301E-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	0.5773	likely_pathogenic	0.6477	pathogenic	-2.101	Highly Destabilizing	0.617	D	0.589	neutral	None	None	None	None	N
F/C	0.3314	likely_benign	0.377	ambiguous	-1.306	Destabilizing	0.99	D	0.644	neutral	N	0.495403542	None	None	N
F/D	0.8927	likely_pathogenic	0.9237	pathogenic	-2.062	Highly Destabilizing	0.92	D	0.658	neutral	None	None	None	None	N
F/E	0.889	likely_pathogenic	0.9188	pathogenic	-1.859	Destabilizing	0.85	D	0.657	neutral	None	None	None	None	N
F/G	0.7857	likely_pathogenic	0.8382	pathogenic	-2.541	Highly Destabilizing	0.92	D	0.654	neutral	None	None	None	None	N
F/H	0.4418	ambiguous	0.4533	ambiguous	-1.101	Destabilizing	0.012	N	0.448	neutral	None	None	None	None	N
F/I	0.3233	likely_benign	0.4106	ambiguous	-0.702	Destabilizing	0.379	N	0.551	neutral	N	0.514712238	None	None	N
F/K	0.6749	likely_pathogenic	0.6976	pathogenic	-1.499	Destabilizing	0.85	D	0.658	neutral	None	None	None	None	N
F/L	0.8121	likely_pathogenic	0.856	pathogenic	-0.702	Destabilizing	0.004	N	0.235	neutral	N	0.432341016	None	None	N
F/M	0.6061	likely_pathogenic	0.6524	pathogenic	-0.546	Destabilizing	0.85	D	0.551	neutral	None	None	None	None	N
F/N	0.7485	likely_pathogenic	0.791	pathogenic	-1.939	Destabilizing	0.85	D	0.657	neutral	None	None	None	None	N
F/P	0.9917	likely_pathogenic	0.9947	pathogenic	-1.173	Destabilizing	0.972	D	0.681	prob.neutral	None	None	None	None	N
F/Q	0.7177	likely_pathogenic	0.7599	pathogenic	-1.828	Destabilizing	0.92	D	0.677	prob.neutral	None	None	None	None	N
F/R	0.4902	ambiguous	0.524	ambiguous	-1.177	Destabilizing	0.85	D	0.657	neutral	None	None	None	None	N
F/S	0.4444	ambiguous	0.525	ambiguous	-2.628	Highly Destabilizing	0.896	D	0.624	neutral	D	0.555420696	None	None	N
F/T	0.6152	likely_pathogenic	0.6867	pathogenic	-2.308	Highly Destabilizing	0.85	D	0.626	neutral	None	None	None	None	N
F/V	0.3108	likely_benign	0.3784	ambiguous	-1.173	Destabilizing	0.379	N	0.571	neutral	N	0.489241008	None	None	N
F/W	0.4362	ambiguous	0.4605	ambiguous	0.161	Stabilizing	0.977	D	0.556	neutral	None	None	None	None	N
F/Y	0.1517	likely_benign	0.1492	benign	-0.142	Destabilizing	0.004	N	0.316	neutral	D	0.53173352	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.