TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7582	22969;22970;22971	chr2:178721919;178721918;178721917	chr2:179586646;179586645;179586644
N2AB	7265	22018;22019;22020	chr2:178721919;178721918;178721917	chr2:179586646;179586645;179586644
N2A	6338	19237;19238;19239	chr2:178721919;178721918;178721917	chr2:179586646;179586645;179586644
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-60
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.3407
• 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
S/C	rs768179623	-0.619	0.883	N	0.695	0.476	0.634587441147	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	4.45E-05	0
S/C	rs768179623	-0.619	0.883	N	0.695	0.476	0.634587441147	gnomAD-4.0.0	1.02655E-05	None	None	None	None	N	None	0	2.23634E-05	None	0	0	None	0	0	1.25953E-05	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
S/A	0.0694	likely_benign	0.068	benign	-0.726	Destabilizing	0.055	N	0.452	neutral	N	0.451654456	None	None	N
S/C	0.18	likely_benign	0.1985	benign	-0.383	Destabilizing	0.883	D	0.695	prob.neutral	N	0.519729382	None	None	N
S/D	0.7134	likely_pathogenic	0.6926	pathogenic	0.249	Stabilizing	0.272	N	0.509	neutral	None	None	None	None	N
S/E	0.7338	likely_pathogenic	0.7233	pathogenic	0.189	Stabilizing	0.272	N	0.506	neutral	None	None	None	None	N
S/F	0.289	likely_benign	0.3144	benign	-1.222	Destabilizing	0.667	D	0.758	deleterious	N	0.516513378	None	None	N
S/G	0.1138	likely_benign	0.1187	benign	-0.881	Destabilizing	0.001	N	0.2	neutral	None	None	None	None	N
S/H	0.6155	likely_pathogenic	0.6135	pathogenic	-1.416	Destabilizing	0.968	D	0.681	prob.neutral	None	None	None	None	N
S/I	0.2545	likely_benign	0.3031	benign	-0.433	Destabilizing	0.396	N	0.735	prob.delet.	None	None	None	None	N
S/K	0.8536	likely_pathogenic	0.8581	pathogenic	-0.442	Destabilizing	0.272	N	0.498	neutral	None	None	None	None	N
S/L	0.1192	likely_benign	0.1308	benign	-0.433	Destabilizing	0.157	N	0.641	neutral	None	None	None	None	N
S/M	0.2213	likely_benign	0.2534	benign	-0.019	Destabilizing	0.909	D	0.681	prob.neutral	None	None	None	None	N
S/N	0.2777	likely_benign	0.2702	benign	-0.229	Destabilizing	0.272	N	0.519	neutral	None	None	None	None	N
S/P	0.8335	likely_pathogenic	0.8688	pathogenic	-0.502	Destabilizing	0.667	D	0.696	prob.neutral	D	0.522843254	None	None	N
S/Q	0.6796	likely_pathogenic	0.6844	pathogenic	-0.484	Destabilizing	0.726	D	0.541	neutral	None	None	None	None	N
S/R	0.7571	likely_pathogenic	0.7611	pathogenic	-0.308	Destabilizing	0.567	D	0.697	prob.neutral	None	None	None	None	N
S/T	0.0936	likely_benign	0.1117	benign	-0.386	Destabilizing	None	N	0.162	neutral	N	0.513377705	None	None	N
S/V	0.2399	likely_benign	0.2954	benign	-0.502	Destabilizing	0.157	N	0.639	neutral	None	None	None	None	N
S/W	0.5572	ambiguous	0.5708	pathogenic	-1.139	Destabilizing	0.968	D	0.791	deleterious	None	None	None	None	N
S/Y	0.3331	likely_benign	0.3508	ambiguous	-0.882	Destabilizing	0.667	D	0.755	deleterious	N	0.519475892	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.