TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23327	70204;70205;70206	chr2:178576153;178576152;178576151	chr2:179440880;179440879;179440878
N2AB	21686	65281;65282;65283	chr2:178576153;178576152;178576151	chr2:179440880;179440879;179440878
N2A	20759	62500;62501;62502	chr2:178576153;178576152;178576151	chr2:179440880;179440879;179440878
N2B	14262	43009;43010;43011	chr2:178576153;178576152;178576151	chr2:179440880;179440879;179440878
Novex-1	14387	43384;43385;43386	chr2:178576153;178576152;178576151	chr2:179440880;179440879;179440878
Novex-2	14454	43585;43586;43587	chr2:178576153;178576152;178576151	chr2:179440880;179440879;179440878
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-57
• Domain position: 88
• Structural Position: 120
• Q(SASA): 0.318
• 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
P/S	None	None	1.0	N	0.726	0.375	0.339316883193	gnomAD-4.0.0	3.18491E-06	None	None	None	None	I	None	1.13225E-04	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
P/A	0.0975	likely_benign	0.0925	benign	-1.097	Destabilizing	1.0	D	0.697	prob.neutral	N	0.469327642	None	None	I
P/C	0.5901	likely_pathogenic	0.5637	ambiguous	-0.726	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
P/D	0.6984	likely_pathogenic	0.6948	pathogenic	-0.891	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
P/E	0.5739	likely_pathogenic	0.5614	ambiguous	-0.968	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
P/F	0.5827	likely_pathogenic	0.5707	pathogenic	-1.025	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
P/G	0.4873	ambiguous	0.4615	ambiguous	-1.318	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	I
P/H	0.3168	likely_benign	0.2968	benign	-0.838	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
P/I	0.6363	likely_pathogenic	0.6243	pathogenic	-0.629	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
P/K	0.6667	likely_pathogenic	0.6329	pathogenic	-0.947	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
P/L	0.3237	likely_benign	0.3225	benign	-0.629	Destabilizing	1.0	D	0.803	deleterious	D	0.532679308	None	None	I
P/M	0.5124	ambiguous	0.507	ambiguous	-0.464	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
P/N	0.5838	likely_pathogenic	0.5772	pathogenic	-0.604	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
P/Q	0.4217	ambiguous	0.4016	ambiguous	-0.871	Destabilizing	1.0	D	0.775	deleterious	N	0.516602969	None	None	I
P/R	0.5383	ambiguous	0.5052	ambiguous	-0.342	Destabilizing	1.0	D	0.834	deleterious	D	0.534200245	None	None	I
P/S	0.1948	likely_benign	0.1971	benign	-1.025	Destabilizing	1.0	D	0.726	prob.delet.	N	0.501599359	None	None	I
P/T	0.2322	likely_benign	0.2304	benign	-1.005	Destabilizing	1.0	D	0.723	prob.delet.	N	0.507955688	None	None	I
P/V	0.4342	ambiguous	0.4274	ambiguous	-0.75	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/W	0.771	likely_pathogenic	0.7508	pathogenic	-1.111	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
P/Y	0.5634	ambiguous	0.5433	ambiguous	-0.854	Destabilizing	1.0	D	0.853	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.