TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25802	77629;77630;77631	chr2:178568728;178568727;178568726	chr2:179433455;179433454;179433453
N2AB	24161	72706;72707;72708	chr2:178568728;178568727;178568726	chr2:179433455;179433454;179433453
N2A	23234	69925;69926;69927	chr2:178568728;178568727;178568726	chr2:179433455;179433454;179433453
N2B	16737	50434;50435;50436	chr2:178568728;178568727;178568726	chr2:179433455;179433454;179433453
Novex-1	16862	50809;50810;50811	chr2:178568728;178568727;178568726	chr2:179433455;179433454;179433453
Novex-2	16929	51010;51011;51012	chr2:178568728;178568727;178568726	chr2:179433455;179433454;179433453
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-136
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.2835
• 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
P/L	None	None	0.014	N	0.456	0.217	0.321672782286	gnomAD-4.0.0	2.05337E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69898E-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
P/A	0.1263	likely_benign	0.1276	benign	-1.248	Destabilizing	0.058	N	0.359	neutral	N	0.506981224	None	None	N
P/C	0.6518	likely_pathogenic	0.6704	pathogenic	-0.866	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	N
P/D	0.865	likely_pathogenic	0.8667	pathogenic	-1.171	Destabilizing	0.978	D	0.55	neutral	None	None	None	None	N
P/E	0.6742	likely_pathogenic	0.6706	pathogenic	-1.108	Destabilizing	0.978	D	0.52	neutral	None	None	None	None	N
P/F	0.7179	likely_pathogenic	0.7226	pathogenic	-0.785	Destabilizing	0.956	D	0.668	neutral	None	None	None	None	N
P/G	0.5761	likely_pathogenic	0.5939	pathogenic	-1.61	Destabilizing	0.86	D	0.568	neutral	None	None	None	None	N
P/H	0.5609	ambiguous	0.5707	pathogenic	-1.177	Destabilizing	0.997	D	0.639	neutral	N	0.4726046	None	None	N
P/I	0.322	likely_benign	0.3289	benign	-0.336	Destabilizing	0.915	D	0.607	neutral	None	None	None	None	N
P/K	0.699	likely_pathogenic	0.7051	pathogenic	-1.134	Destabilizing	0.956	D	0.517	neutral	None	None	None	None	N
P/L	0.123	likely_benign	0.1299	benign	-0.336	Destabilizing	0.014	N	0.456	neutral	N	0.428557726	None	None	N
P/M	0.3422	ambiguous	0.3436	ambiguous	-0.383	Destabilizing	0.988	D	0.639	neutral	None	None	None	None	N
P/N	0.7251	likely_pathogenic	0.7298	pathogenic	-1.081	Destabilizing	0.978	D	0.631	neutral	None	None	None	None	N
P/Q	0.4722	ambiguous	0.4709	ambiguous	-1.125	Destabilizing	0.993	D	0.597	neutral	None	None	None	None	N
P/R	0.5912	likely_pathogenic	0.6007	pathogenic	-0.769	Destabilizing	0.97	D	0.628	neutral	N	0.463993319	None	None	N
P/S	0.3668	ambiguous	0.374	ambiguous	-1.589	Destabilizing	0.698	D	0.537	neutral	N	0.456106507	None	None	N
P/T	0.1805	likely_benign	0.1778	benign	-1.404	Destabilizing	0.058	N	0.354	neutral	N	0.490395618	None	None	N
P/V	0.1941	likely_benign	0.2011	benign	-0.605	Destabilizing	0.754	D	0.577	neutral	None	None	None	None	N
P/W	0.8651	likely_pathogenic	0.8754	pathogenic	-1.078	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
P/Y	0.7029	likely_pathogenic	0.7174	pathogenic	-0.717	Destabilizing	0.978	D	0.669	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.