TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20511	61756;61757;61758	chr2:178590194;178590193;178590192	chr2:179454921;179454920;179454919
N2AB	18870	56833;56834;56835	chr2:178590194;178590193;178590192	chr2:179454921;179454920;179454919
N2A	17943	54052;54053;54054	chr2:178590194;178590193;178590192	chr2:179454921;179454920;179454919
N2B	11446	34561;34562;34563	chr2:178590194;178590193;178590192	chr2:179454921;179454920;179454919
Novex-1	11571	34936;34937;34938	chr2:178590194;178590193;178590192	chr2:179454921;179454920;179454919
Novex-2	11638	35137;35138;35139	chr2:178590194;178590193;178590192	chr2:179454921;179454920;179454919
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-121
• Domain position: 33
• Structural Position: 49
• Q(SASA): 0.1912
• 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
T/A	None	None	None	N	0.151	0.112	0.0846915920261	gnomAD-4.0.0	6.85972E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00859E-07	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
T/A	0.0933	likely_benign	0.0889	benign	-1.247	Destabilizing	None	N	0.151	neutral	N	0.510157602	None	None	I
T/C	0.2738	likely_benign	0.2494	benign	-0.691	Destabilizing	0.356	N	0.529	neutral	None	None	None	None	I
T/D	0.5245	ambiguous	0.5244	ambiguous	-0.555	Destabilizing	0.016	N	0.47	neutral	None	None	None	None	I
T/E	0.338	likely_benign	0.3576	ambiguous	-0.395	Destabilizing	0.016	N	0.473	neutral	None	None	None	None	I
T/F	0.2296	likely_benign	0.221	benign	-1.046	Destabilizing	None	N	0.283	neutral	None	None	None	None	I
T/G	0.2037	likely_benign	0.1937	benign	-1.625	Destabilizing	0.007	N	0.419	neutral	None	None	None	None	I
T/H	0.2698	likely_benign	0.2592	benign	-1.651	Destabilizing	0.356	N	0.559	neutral	None	None	None	None	I
T/I	0.2046	likely_benign	0.2081	benign	-0.269	Destabilizing	0.012	N	0.463	neutral	N	0.495900226	None	None	I
T/K	0.3179	likely_benign	0.348	ambiguous	-0.207	Destabilizing	0.016	N	0.465	neutral	None	None	None	None	I
T/L	0.1031	likely_benign	0.0947	benign	-0.269	Destabilizing	0.007	N	0.413	neutral	None	None	None	None	I
T/M	0.0923	likely_benign	0.0821	benign	-0.207	Destabilizing	0.356	N	0.532	neutral	None	None	None	None	I
T/N	0.1305	likely_benign	0.1241	benign	-0.65	Destabilizing	0.012	N	0.376	neutral	N	0.455616435	None	None	I
T/P	0.8626	likely_pathogenic	0.8913	pathogenic	-0.564	Destabilizing	0.055	N	0.525	neutral	N	0.47874712	None	None	I
T/Q	0.2177	likely_benign	0.2246	benign	-0.554	Destabilizing	0.072	N	0.52	neutral	None	None	None	None	I
T/R	0.268	likely_benign	0.3056	benign	-0.349	Destabilizing	0.072	N	0.53	neutral	None	None	None	None	I
T/S	0.085	likely_benign	0.0779	benign	-1.057	Destabilizing	None	N	0.134	neutral	N	0.441932455	None	None	I
T/V	0.1663	likely_benign	0.1595	benign	-0.564	Destabilizing	0.016	N	0.395	neutral	None	None	None	None	I
T/W	0.5354	ambiguous	0.5042	ambiguous	-1.006	Destabilizing	0.864	D	0.547	neutral	None	None	None	None	I
T/Y	0.251	likely_benign	0.2319	benign	-0.681	Destabilizing	0.038	N	0.544	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.