TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7684	23275;23276;23277	chr2:178720969;178720968;178720967	chr2:179585696;179585695;179585694
N2AB	7367	22324;22325;22326	chr2:178720969;178720968;178720967	chr2:179585696;179585695;179585694
N2A	6440	19543;19544;19545	chr2:178720969;178720968;178720967	chr2:179585696;179585695;179585694
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: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-61
• Domain position: 77
• Structural Position: 159
• Q(SASA): 0.3419
• 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
H/Y	rs759120198	0.887	0.643	N	0.379	0.24	0.364926071151	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
H/Y	rs759120198	0.887	0.643	N	0.379	0.24	0.364926071151	gnomAD-4.0.0	2.06281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.04311E-07	2.32775E-05	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
H/A	0.2411	likely_benign	0.3453	ambiguous	-0.398	Destabilizing	0.466	N	0.491	neutral	None	None	None	None	N
H/C	0.1602	likely_benign	0.196	benign	0.344	Stabilizing	0.981	D	0.471	neutral	None	None	None	None	N
H/D	0.2352	likely_benign	0.321	benign	-0.174	Destabilizing	0.324	N	0.443	neutral	N	0.458521713	None	None	N
H/E	0.2009	likely_benign	0.2815	benign	-0.124	Destabilizing	0.153	N	0.303	neutral	None	None	None	None	N
H/F	0.2654	likely_benign	0.3602	ambiguous	0.266	Stabilizing	0.805	D	0.48	neutral	None	None	None	None	N
H/G	0.2731	likely_benign	0.3838	ambiguous	-0.717	Destabilizing	0.466	N	0.459	neutral	None	None	None	None	N
H/I	0.2307	likely_benign	0.3267	benign	0.448	Stabilizing	0.296	N	0.549	neutral	None	None	None	None	N
H/K	0.1412	likely_benign	0.1893	benign	-0.309	Destabilizing	0.148	N	0.444	neutral	None	None	None	None	N
H/L	0.1305	likely_benign	0.1723	benign	0.448	Stabilizing	0.001	N	0.303	neutral	N	0.488361831	None	None	N
H/M	0.3983	ambiguous	0.5158	ambiguous	0.379	Stabilizing	0.747	D	0.481	neutral	None	None	None	None	N
H/N	0.119	likely_benign	0.1396	benign	-0.137	Destabilizing	0.324	N	0.263	neutral	N	0.458521713	None	None	N
H/P	0.7283	likely_pathogenic	0.7887	pathogenic	0.19	Stabilizing	0.493	N	0.505	neutral	N	0.516319223	None	None	N
H/Q	0.0962	likely_benign	0.1248	benign	0.002	Stabilizing	0.004	N	0.107	neutral	N	0.413557428	None	None	N
H/R	0.0586	likely_benign	0.0672	benign	-0.743	Destabilizing	0.001	N	0.094	neutral	N	0.419387322	None	None	N
H/S	0.1751	likely_benign	0.2488	benign	-0.175	Destabilizing	0.466	N	0.413	neutral	None	None	None	None	N
H/T	0.1873	likely_benign	0.2776	benign	-0.032	Destabilizing	0.388	N	0.453	neutral	None	None	None	None	N
H/V	0.194	likely_benign	0.2709	benign	0.19	Stabilizing	0.305	N	0.479	neutral	None	None	None	None	N
H/W	0.2808	likely_benign	0.3707	ambiguous	0.367	Stabilizing	0.996	D	0.468	neutral	None	None	None	None	N
H/Y	0.1002	likely_benign	0.13	benign	0.668	Stabilizing	0.643	D	0.379	neutral	N	0.502581922	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.