TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19758	59497;59498;59499	chr2:178592847;178592846;178592845	chr2:179457574;179457573;179457572
N2AB	18117	54574;54575;54576	chr2:178592847;178592846;178592845	chr2:179457574;179457573;179457572
N2A	17190	51793;51794;51795	chr2:178592847;178592846;178592845	chr2:179457574;179457573;179457572
N2B	10693	32302;32303;32304	chr2:178592847;178592846;178592845	chr2:179457574;179457573;179457572
Novex-1	10818	32677;32678;32679	chr2:178592847;178592846;178592845	chr2:179457574;179457573;179457572
Novex-2	10885	32878;32879;32880	chr2:178592847;178592846;178592845	chr2:179457574;179457573;179457572
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-31
• Domain position: 79
• Structural Position: 109
• Q(SASA): 0.0929
• 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
L/S	None	None	0.012	N	0.667	0.117	0.27479166964	gnomAD-4.0.0	7.20193E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.87501E-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
L/A	0.1823	likely_benign	0.1571	benign	-3.056	Highly Destabilizing	0.016	N	0.653	neutral	None	None	None	None	N
L/C	0.2738	likely_benign	0.2754	benign	-2.356	Highly Destabilizing	0.628	D	0.715	prob.delet.	None	None	None	None	N
L/D	0.8142	likely_pathogenic	0.7651	pathogenic	-3.542	Highly Destabilizing	0.072	N	0.741	deleterious	None	None	None	None	N
L/E	0.4275	ambiguous	0.362	ambiguous	-3.358	Highly Destabilizing	0.038	N	0.723	prob.delet.	None	None	None	None	N
L/F	0.1115	likely_benign	0.1061	benign	-1.721	Destabilizing	None	N	0.426	neutral	N	0.39263229	None	None	N
L/G	0.5106	ambiguous	0.464	ambiguous	-3.515	Highly Destabilizing	0.072	N	0.721	prob.delet.	None	None	None	None	N
L/H	0.1688	likely_benign	0.1544	benign	-2.689	Highly Destabilizing	0.356	N	0.746	deleterious	None	None	None	None	N
L/I	0.0948	likely_benign	0.0799	benign	-1.717	Destabilizing	None	N	0.275	neutral	N	0.353863258	None	None	N
L/K	0.1396	likely_benign	0.1253	benign	-2.381	Highly Destabilizing	None	N	0.493	neutral	None	None	None	None	N
L/M	0.0645	likely_benign	0.064	benign	-1.765	Destabilizing	None	N	0.245	neutral	None	None	None	None	N
L/N	0.404	ambiguous	0.3708	ambiguous	-2.661	Highly Destabilizing	0.072	N	0.736	prob.delet.	None	None	None	None	N
L/P	0.9712	likely_pathogenic	0.9522	pathogenic	-2.15	Highly Destabilizing	0.356	N	0.757	deleterious	None	None	None	None	N
L/Q	0.1242	likely_benign	0.1093	benign	-2.601	Highly Destabilizing	0.072	N	0.734	prob.delet.	None	None	None	None	N
L/R	0.1245	likely_benign	0.1076	benign	-1.89	Destabilizing	None	N	0.646	neutral	None	None	None	None	N
L/S	0.1814	likely_benign	0.1553	benign	-3.266	Highly Destabilizing	0.012	N	0.667	neutral	N	0.398307469	None	None	N
L/T	0.1136	likely_benign	0.1062	benign	-2.969	Highly Destabilizing	0.001	N	0.488	neutral	None	None	None	None	N
L/V	0.0787	likely_benign	0.074	benign	-2.15	Highly Destabilizing	0.002	N	0.437	neutral	N	0.407214953	None	None	N
L/W	0.2276	likely_benign	0.1998	benign	-2.034	Highly Destabilizing	0.676	D	0.721	prob.delet.	None	None	None	None	N
L/Y	0.262	likely_benign	0.2596	benign	-1.926	Destabilizing	0.001	N	0.611	neutral	None	None	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.