TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16494	49705;49706;49707	chr2:178613803;178613802;178613801	chr2:179478530;179478529;179478528
N2AB	14853	44782;44783;44784	chr2:178613803;178613802;178613801	chr2:179478530;179478529;179478528
N2A	13926	42001;42002;42003	chr2:178613803;178613802;178613801	chr2:179478530;179478529;179478528
N2B	7429	22510;22511;22512	chr2:178613803;178613802;178613801	chr2:179478530;179478529;179478528
Novex-1	7554	22885;22886;22887	chr2:178613803;178613802;178613801	chr2:179478530;179478529;179478528
Novex-2	7621	23086;23087;23088	chr2:178613803;178613802;178613801	chr2:179478530;179478529;179478528
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-7
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.244
• 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
T/K	rs1576450617	None	0.062	N	0.279	0.081	0.225215365344	gnomAD-4.0.0	1.59374E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86356E-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
T/A	0.1066	likely_benign	0.0958	benign	-0.4	Destabilizing	0.027	N	0.293	neutral	N	0.466296708	None	None	N
T/C	0.4054	ambiguous	0.3457	ambiguous	-0.238	Destabilizing	0.824	D	0.289	neutral	None	None	None	None	N
T/D	0.4212	ambiguous	0.38	ambiguous	-0.147	Destabilizing	0.081	N	0.266	neutral	None	None	None	None	N
T/E	0.4401	ambiguous	0.4244	ambiguous	-0.223	Destabilizing	0.035	N	0.301	neutral	None	None	None	None	N
T/F	0.4212	ambiguous	0.3984	ambiguous	-0.823	Destabilizing	0.555	D	0.351	neutral	None	None	None	None	N
T/G	0.1949	likely_benign	0.1503	benign	-0.547	Destabilizing	0.081	N	0.26	neutral	None	None	None	None	N
T/H	0.3037	likely_benign	0.279	benign	-0.849	Destabilizing	0.001	N	0.221	neutral	None	None	None	None	N
T/I	0.3826	ambiguous	0.3384	benign	-0.129	Destabilizing	0.317	N	0.303	neutral	D	0.538813297	None	None	N
T/K	0.335	likely_benign	0.3531	ambiguous	-0.528	Destabilizing	0.062	N	0.279	neutral	N	0.472238645	None	None	N
T/L	0.1577	likely_benign	0.1425	benign	-0.129	Destabilizing	0.149	N	0.282	neutral	None	None	None	None	N
T/M	0.1406	likely_benign	0.137	benign	0.134	Stabilizing	0.555	D	0.274	neutral	None	None	None	None	N
T/N	0.1029	likely_benign	0.0909	benign	-0.286	Destabilizing	0.081	N	0.285	neutral	None	None	None	None	N
T/P	0.6226	likely_pathogenic	0.618	pathogenic	-0.191	Destabilizing	0.317	N	0.297	neutral	N	0.469895506	None	None	N
T/Q	0.3062	likely_benign	0.2781	benign	-0.556	Destabilizing	0.002	N	0.23	neutral	None	None	None	None	N
T/R	0.3155	likely_benign	0.3539	ambiguous	-0.181	Destabilizing	0.062	N	0.299	neutral	N	0.468746047	None	None	N
T/S	0.0869	likely_benign	0.0762	benign	-0.468	Destabilizing	None	N	0.189	neutral	N	0.389816962	None	None	N
T/V	0.2852	likely_benign	0.2396	benign	-0.191	Destabilizing	0.149	N	0.273	neutral	None	None	None	None	N
T/W	0.7283	likely_pathogenic	0.7233	pathogenic	-0.818	Destabilizing	0.935	D	0.383	neutral	None	None	None	None	N
T/Y	0.3985	ambiguous	0.3812	ambiguous	-0.56	Destabilizing	0.38	N	0.334	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.