TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4717	14374;14375;14376	chr2:178738304;178738303;178738302	chr2:179603031;179603030;179603029
N2AB	4400	13423;13424;13425	chr2:178738304;178738303;178738302	chr2:179603031;179603030;179603029
N2A	3473	10642;10643;10644	chr2:178738304;178738303;178738302	chr2:179603031;179603030;179603029
N2B	4354	13285;13286;13287	chr2:178738304;178738303;178738302	chr2:179603031;179603030;179603029
Novex-1	4479	13660;13661;13662	chr2:178738304;178738303;178738302	chr2:179603031;179603030;179603029
Novex-2	4546	13861;13862;13863	chr2:178738304;178738303;178738302	chr2:179603031;179603030;179603029
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-30
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1435
• 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
A/D	None	None	0.991	D	0.807	0.425	0.529361283073	gnomAD-4.0.0	6.84348E-07	None	None	None	None	I	None	0	0	None	0	0	None	1.87378E-05	0	0	0	0
A/V	None	None	0.322	N	0.335	0.149	0.228597637076	gnomAD-4.0.0	6.84348E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99543E-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
A/C	0.8543	likely_pathogenic	0.8967	pathogenic	-0.705	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	I
A/D	0.9955	likely_pathogenic	0.9947	pathogenic	-1.468	Destabilizing	0.991	D	0.807	deleterious	D	0.662703319	None	None	I
A/E	0.9872	likely_pathogenic	0.986	pathogenic	-1.291	Destabilizing	0.993	D	0.79	deleterious	None	None	None	None	I
A/F	0.9675	likely_pathogenic	0.9761	pathogenic	-0.53	Destabilizing	0.993	D	0.813	deleterious	None	None	None	None	I
A/G	0.3565	ambiguous	0.3962	ambiguous	-1.253	Destabilizing	0.046	N	0.288	neutral	N	0.454879285	None	None	I
A/H	0.9941	likely_pathogenic	0.9947	pathogenic	-1.569	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	I
A/I	0.871	likely_pathogenic	0.8946	pathogenic	0.429	Stabilizing	0.973	D	0.774	deleterious	None	None	None	None	I
A/K	0.9968	likely_pathogenic	0.9961	pathogenic	-0.977	Destabilizing	0.993	D	0.791	deleterious	None	None	None	None	I
A/L	0.7882	likely_pathogenic	0.8065	pathogenic	0.429	Stabilizing	0.91	D	0.673	neutral	None	None	None	None	I
A/M	0.8982	likely_pathogenic	0.9175	pathogenic	0.257	Stabilizing	0.998	D	0.772	deleterious	None	None	None	None	I
A/N	0.9853	likely_pathogenic	0.9868	pathogenic	-1.165	Destabilizing	0.986	D	0.801	deleterious	None	None	None	None	I
A/P	0.9821	likely_pathogenic	0.9817	pathogenic	0.069	Stabilizing	0.997	D	0.8	deleterious	D	0.601561893	None	None	I
A/Q	0.9754	likely_pathogenic	0.975	pathogenic	-0.985	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	I
A/R	0.9883	likely_pathogenic	0.9858	pathogenic	-1.074	Destabilizing	0.993	D	0.791	deleterious	None	None	None	None	I
A/S	0.3803	ambiguous	0.4327	ambiguous	-1.637	Destabilizing	0.939	D	0.575	neutral	D	0.584465041	None	None	I
A/T	0.5352	ambiguous	0.6277	pathogenic	-1.313	Destabilizing	0.939	D	0.616	neutral	N	0.485630953	None	None	I
A/V	0.5395	ambiguous	0.6197	pathogenic	0.069	Stabilizing	0.322	N	0.335	neutral	N	0.426832019	None	None	I
A/W	0.9978	likely_pathogenic	0.9979	pathogenic	-1.216	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	I
A/Y	0.9916	likely_pathogenic	0.9922	pathogenic	-0.597	Destabilizing	0.998	D	0.815	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.