TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26714	80365;80366;80367	chr2:178565992;178565991;178565990	chr2:179430719;179430718;179430717
N2AB	25073	75442;75443;75444	chr2:178565992;178565991;178565990	chr2:179430719;179430718;179430717
N2A	24146	72661;72662;72663	chr2:178565992;178565991;178565990	chr2:179430719;179430718;179430717
N2B	17649	53170;53171;53172	chr2:178565992;178565991;178565990	chr2:179430719;179430718;179430717
Novex-1	17774	53545;53546;53547	chr2:178565992;178565991;178565990	chr2:179430719;179430718;179430717
Novex-2	17841	53746;53747;53748	chr2:178565992;178565991;178565990	chr2:179430719;179430718;179430717
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-82
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.9592
• 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/N	None	None	0.887	N	0.452	0.13	0.202949470691	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-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
K/A	0.4733	ambiguous	0.4849	ambiguous	0.047	Stabilizing	0.231	N	0.538	neutral	None	None	None	None	I
K/C	0.8272	likely_pathogenic	0.8381	pathogenic	-0.15	Destabilizing	0.992	D	0.589	neutral	None	None	None	None	I
K/D	0.8353	likely_pathogenic	0.8454	pathogenic	-0.055	Destabilizing	0.912	D	0.519	neutral	None	None	None	None	I
K/E	0.4855	ambiguous	0.4751	ambiguous	-0.048	Destabilizing	0.248	N	0.506	neutral	N	0.462028086	None	None	I
K/F	0.9125	likely_pathogenic	0.9176	pathogenic	-0.127	Destabilizing	0.671	D	0.593	neutral	None	None	None	None	I
K/G	0.7226	likely_pathogenic	0.7196	pathogenic	-0.153	Destabilizing	0.747	D	0.576	neutral	None	None	None	None	I
K/H	0.475	ambiguous	0.501	ambiguous	-0.37	Destabilizing	0.929	D	0.538	neutral	None	None	None	None	I
K/I	0.578	likely_pathogenic	0.5836	pathogenic	0.497	Stabilizing	0.021	N	0.537	neutral	None	None	None	None	I
K/L	0.5887	likely_pathogenic	0.5831	pathogenic	0.497	Stabilizing	0.021	N	0.566	neutral	None	None	None	None	I
K/M	0.4956	ambiguous	0.4849	ambiguous	0.216	Stabilizing	0.483	N	0.543	neutral	N	0.478409904	None	None	I
K/N	0.7599	likely_pathogenic	0.7708	pathogenic	0.252	Stabilizing	0.887	D	0.452	neutral	N	0.490486911	None	None	I
K/P	0.5213	ambiguous	0.541	ambiguous	0.375	Stabilizing	0.969	D	0.553	neutral	None	None	None	None	I
K/Q	0.2709	likely_benign	0.2724	benign	0.085	Stabilizing	0.318	N	0.487	neutral	N	0.515459926	None	None	I
K/R	0.075	likely_benign	0.0757	benign	-0.019	Destabilizing	None	N	0.15	neutral	N	0.460126718	None	None	I
K/S	0.6977	likely_pathogenic	0.7006	pathogenic	-0.19	Destabilizing	0.747	D	0.501	neutral	None	None	None	None	I
K/T	0.4191	ambiguous	0.4147	ambiguous	-0.04	Destabilizing	0.248	N	0.555	neutral	N	0.506936444	None	None	I
K/V	0.4698	ambiguous	0.4711	ambiguous	0.375	Stabilizing	None	N	0.411	neutral	None	None	None	None	I
K/W	0.881	likely_pathogenic	0.8831	pathogenic	-0.162	Destabilizing	0.994	D	0.648	neutral	None	None	None	None	I
K/Y	0.8321	likely_pathogenic	0.8393	pathogenic	0.181	Stabilizing	0.326	N	0.593	neutral	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.