TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23582	70969;70970;70971	chr2:178575388;178575387;178575386	chr2:179440115;179440114;179440113
N2AB	21941	66046;66047;66048	chr2:178575388;178575387;178575386	chr2:179440115;179440114;179440113
N2A	21014	63265;63266;63267	chr2:178575388;178575387;178575386	chr2:179440115;179440114;179440113
N2B	14517	43774;43775;43776	chr2:178575388;178575387;178575386	chr2:179440115;179440114;179440113
Novex-1	14642	44149;44150;44151	chr2:178575388;178575387;178575386	chr2:179440115;179440114;179440113
Novex-2	14709	44350;44351;44352	chr2:178575388;178575387;178575386	chr2:179440115;179440114;179440113
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-59
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.1946
• 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
I/L	rs1305914437	-0.681	0.016	N	0.322	0.115	0.417586769301	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
I/L	rs1305914437	-0.681	0.016	N	0.322	0.115	0.417586769301	gnomAD-4.0.0	3.18338E-06	None	None	None	None	N	None	5.65739E-05	0	None	0	2.77855E-05	None	0	0	0	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
I/A	0.5399	ambiguous	0.5052	ambiguous	-1.418	Destabilizing	0.25	N	0.485	neutral	None	None	None	None	N
I/C	0.6349	likely_pathogenic	0.6369	pathogenic	-0.764	Destabilizing	0.992	D	0.554	neutral	None	None	None	None	N
I/D	0.9245	likely_pathogenic	0.9186	pathogenic	-1.011	Destabilizing	0.972	D	0.608	neutral	None	None	None	None	N
I/E	0.859	likely_pathogenic	0.8412	pathogenic	-1.04	Destabilizing	0.92	D	0.611	neutral	None	None	None	None	N
I/F	0.2177	likely_benign	0.2076	benign	-1.078	Destabilizing	0.004	N	0.316	neutral	N	0.469802207	None	None	N
I/G	0.8515	likely_pathogenic	0.8281	pathogenic	-1.699	Destabilizing	0.766	D	0.566	neutral	None	None	None	None	N
I/H	0.7301	likely_pathogenic	0.7325	pathogenic	-0.887	Destabilizing	0.992	D	0.603	neutral	None	None	None	None	N
I/K	0.7294	likely_pathogenic	0.7338	pathogenic	-0.997	Destabilizing	0.85	D	0.601	neutral	None	None	None	None	N
I/L	0.1252	likely_benign	0.1334	benign	-0.736	Destabilizing	0.016	N	0.322	neutral	N	0.422837767	None	None	N
I/M	0.1296	likely_benign	0.1285	benign	-0.521	Destabilizing	0.016	N	0.215	neutral	N	0.474037378	None	None	N
I/N	0.6348	likely_pathogenic	0.5929	pathogenic	-0.775	Destabilizing	0.896	D	0.609	neutral	N	0.5113049	None	None	N
I/P	0.9523	likely_pathogenic	0.9443	pathogenic	-0.931	Destabilizing	0.972	D	0.609	neutral	None	None	None	None	N
I/Q	0.7155	likely_pathogenic	0.7136	pathogenic	-0.986	Destabilizing	0.92	D	0.608	neutral	None	None	None	None	N
I/R	0.6518	likely_pathogenic	0.6535	pathogenic	-0.338	Destabilizing	0.85	D	0.611	neutral	None	None	None	None	N
I/S	0.5837	likely_pathogenic	0.548	ambiguous	-1.295	Destabilizing	0.549	D	0.546	neutral	N	0.440847524	None	None	N
I/T	0.4874	ambiguous	0.4559	ambiguous	-1.211	Destabilizing	0.549	D	0.511	neutral	N	0.45583562	None	None	N
I/V	0.0784	likely_benign	0.0721	benign	-0.931	Destabilizing	0.001	N	0.159	neutral	N	0.353516541	None	None	N
I/W	0.8756	likely_pathogenic	0.8832	pathogenic	-1.137	Destabilizing	0.992	D	0.609	neutral	None	None	None	None	N
I/Y	0.6374	likely_pathogenic	0.6255	pathogenic	-0.92	Destabilizing	0.739	D	0.562	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.