TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23787	71584;71585;71586	chr2:178574773;178574772;178574771	chr2:179439500;179439499;179439498
N2AB	22146	66661;66662;66663	chr2:178574773;178574772;178574771	chr2:179439500;179439499;179439498
N2A	21219	63880;63881;63882	chr2:178574773;178574772;178574771	chr2:179439500;179439499;179439498
N2B	14722	44389;44390;44391	chr2:178574773;178574772;178574771	chr2:179439500;179439499;179439498
Novex-1	14847	44764;44765;44766	chr2:178574773;178574772;178574771	chr2:179439500;179439499;179439498
Novex-2	14914	44965;44966;44967	chr2:178574773;178574772;178574771	chr2:179439500;179439499;179439498
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: Fn3-60
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.2944
• 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	None	None	0.999	N	0.604	0.452	0.296329037015	gnomAD-4.0.0	8.40225E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.18751E-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	0.9721	likely_pathogenic	0.9697	pathogenic	-0.723	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	I
K/C	0.9711	likely_pathogenic	0.9691	pathogenic	-0.779	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
K/D	0.9938	likely_pathogenic	0.994	pathogenic	-0.176	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
K/E	0.9408	likely_pathogenic	0.9415	pathogenic	0.001	Stabilizing	0.999	D	0.604	neutral	N	0.508397881	None	None	I
K/F	0.9945	likely_pathogenic	0.9935	pathogenic	-0.273	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
K/G	0.9851	likely_pathogenic	0.9831	pathogenic	-1.115	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
K/H	0.7963	likely_pathogenic	0.7772	pathogenic	-1.15	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
K/I	0.9363	likely_pathogenic	0.9287	pathogenic	0.322	Stabilizing	1.0	D	0.851	deleterious	N	0.466088866	None	None	I
K/L	0.9347	likely_pathogenic	0.9352	pathogenic	0.322	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
K/M	0.8864	likely_pathogenic	0.8813	pathogenic	-0.044	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
K/N	0.9852	likely_pathogenic	0.9833	pathogenic	-0.742	Destabilizing	1.0	D	0.739	prob.delet.	N	0.519961669	None	None	I
K/P	0.9918	likely_pathogenic	0.991	pathogenic	0.001	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
K/Q	0.6918	likely_pathogenic	0.6645	pathogenic	-0.641	Destabilizing	1.0	D	0.709	prob.delet.	N	0.46707637	None	None	I
K/R	0.1213	likely_benign	0.1127	benign	-0.428	Destabilizing	0.999	D	0.577	neutral	N	0.485830453	None	None	I
K/S	0.9809	likely_pathogenic	0.9796	pathogenic	-1.382	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	I
K/T	0.8831	likely_pathogenic	0.8752	pathogenic	-0.98	Destabilizing	1.0	D	0.814	deleterious	N	0.451904306	None	None	I
K/V	0.9128	likely_pathogenic	0.9063	pathogenic	0.001	Stabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
K/W	0.9888	likely_pathogenic	0.9867	pathogenic	-0.2	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
K/Y	0.9761	likely_pathogenic	0.9742	pathogenic	0.106	Stabilizing	1.0	D	0.825	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.