TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17389	52390;52391;52392	chr2:178608846;178608845;178608844	chr2:179473573;179473572;179473571
N2AB	15748	47467;47468;47469	chr2:178608846;178608845;178608844	chr2:179473573;179473572;179473571
N2A	14821	44686;44687;44688	chr2:178608846;178608845;178608844	chr2:179473573;179473572;179473571
N2B	8324	25195;25196;25197	chr2:178608846;178608845;178608844	chr2:179473573;179473572;179473571
Novex-1	8449	25570;25571;25572	chr2:178608846;178608845;178608844	chr2:179473573;179473572;179473571
Novex-2	8516	25771;25772;25773	chr2:178608846;178608845;178608844	chr2:179473573;179473572;179473571
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-14
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.5134
• 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
K/E	rs779439447	-1.29	0.996	N	0.47	0.36	0.272205846399	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/E	rs779439447	-1.29	0.996	N	0.47	0.36	0.272205846399	gnomAD-4.0.0	1.5947E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43316E-05	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
K/A	0.4297	ambiguous	0.44	ambiguous	-0.972	Destabilizing	0.998	D	0.575	neutral	None	None	None	None	I
K/C	0.557	ambiguous	0.5333	ambiguous	-1.027	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
K/D	0.8141	likely_pathogenic	0.8188	pathogenic	-1.44	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
K/E	0.3187	likely_benign	0.3443	ambiguous	-1.188	Destabilizing	0.996	D	0.47	neutral	N	0.43892194	None	None	I
K/F	0.7711	likely_pathogenic	0.7591	pathogenic	-0.14	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
K/G	0.6436	likely_pathogenic	0.6233	pathogenic	-1.439	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
K/H	0.2638	likely_benign	0.2615	benign	-1.617	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
K/I	0.3254	likely_benign	0.3467	ambiguous	0.329	Stabilizing	1.0	D	0.826	deleterious	N	0.501511981	None	None	I
K/L	0.36	ambiguous	0.3662	ambiguous	0.329	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
K/M	0.2392	likely_benign	0.2562	benign	-0.025	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
K/N	0.5386	ambiguous	0.5548	ambiguous	-1.606	Destabilizing	0.999	D	0.676	prob.neutral	N	0.44284768	None	None	I
K/P	0.9828	likely_pathogenic	0.9775	pathogenic	-0.081	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
K/Q	0.1455	likely_benign	0.1437	benign	-1.284	Destabilizing	0.999	D	0.659	neutral	N	0.448157499	None	None	I
K/R	0.08	likely_benign	0.0763	benign	-1.213	Destabilizing	0.884	D	0.391	neutral	N	0.431822609	None	None	I
K/S	0.428	ambiguous	0.4409	ambiguous	-2.026	Highly Destabilizing	0.998	D	0.569	neutral	None	None	None	None	I
K/T	0.163	likely_benign	0.1765	benign	-1.544	Destabilizing	0.999	D	0.758	deleterious	N	0.382279223	None	None	I
K/V	0.2987	likely_benign	0.3147	benign	-0.081	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
K/W	0.7634	likely_pathogenic	0.7318	pathogenic	-0.29	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
K/Y	0.6266	likely_pathogenic	0.6142	pathogenic	0.055	Stabilizing	1.0	D	0.823	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.