TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26621	80086;80087;80088	chr2:178566271;178566270;178566269	chr2:179430998;179430997;179430996
N2AB	24980	75163;75164;75165	chr2:178566271;178566270;178566269	chr2:179430998;179430997;179430996
N2A	24053	72382;72383;72384	chr2:178566271;178566270;178566269	chr2:179430998;179430997;179430996
N2B	17556	52891;52892;52893	chr2:178566271;178566270;178566269	chr2:179430998;179430997;179430996
Novex-1	17681	53266;53267;53268	chr2:178566271;178566270;178566269	chr2:179430998;179430997;179430996
Novex-2	17748	53467;53468;53469	chr2:178566271;178566270;178566269	chr2:179430998;179430997;179430996
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACG
• RefSeq wild type template codon: TGC
• Domain: Ig-138
• Domain position: 28
• Structural Position: 43
• Q(SASA): 0.3569
• 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/A	rs372537578	-0.616	0.001	N	0.105	0.085	None	gnomAD-2.1.1	3.92E-05	None	None	None	None	N	None	3.71993E-04	5.66E-05	None	0	0	None	0	None	0	0	0
T/A	rs372537578	-0.616	0.001	N	0.105	0.085	None	gnomAD-3.1.2	9.2E-05	None	None	None	None	N	None	3.37773E-04	0	0	0	0	None	0	0	0	0	0
T/A	rs372537578	-0.616	0.001	N	0.105	0.085	None	gnomAD-4.0.0	1.67329E-05	None	None	None	None	N	None	2.93701E-04	3.33511E-05	None	0	0	None	0	0	1.69532E-06	0	1.60128E-05
T/K	rs3731746	-0.677	0.579	N	0.445	0.22	0.377799810692	gnomAD-2.1.1	4.42E-05	None	None	None	None	N	None	0	2.0284E-04	None	0	0	None	0	None	0	2.66E-05	1.65453E-04
T/K	rs3731746	-0.677	0.579	N	0.445	0.22	0.377799810692	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	4.78469E-04
T/K	rs3731746	-0.677	0.579	N	0.445	0.22	0.377799810692	gnomAD-4.0.0	3.28478E-05	None	None	None	None	N	None	2.66894E-05	1.00037E-04	None	0	0	None	0	0	3.56023E-05	0	4.80231E-05
T/M	rs3731746	-0.031	0.914	N	0.476	0.291	None	gnomAD-2.1.1	2.33214E-01	None	None	None	None	N	None	3.36793E-01	1.85994E-01	None	2.28107E-01	6.12878E-01	None	3.03412E-01	None	1.71279E-01	1.66019E-01	2.08696E-01
T/M	rs3731746	-0.031	0.914	N	0.476	0.291	None	gnomAD-3.1.2	2.3958E-01	None	None	None	None	N	None	3.37068E-01	1.8622E-01	4.81319E-01	2.28374E-01	6.13769E-01	None	1.81681E-01	1.83544E-01	1.66353E-01	3.06131E-01	2.22701E-01
T/M	rs3731746	-0.031	0.914	N	0.476	0.291	None	1000 genomes	3.42252E-01	None	None	None	None	N	None	3.442E-01	2.061E-01	None	None	6.29E-01	1.71E-01	None	None	None	3.17E-01	None
T/M	rs3731746	-0.031	0.914	N	0.476	0.291	None	gnomAD-4.0.0	1.93829E-01	None	None	None	None	N	None	3.38459E-01	1.88344E-01	None	2.277E-01	6.15472E-01	None	1.71342E-01	2.28713E-01	1.59595E-01	3.00163E-01	2.14014E-01

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	0.0572	likely_benign	0.0597	benign	-0.731	Destabilizing	0.001	N	0.105	neutral	N	0.464775682	None	None	N
T/C	0.3236	likely_benign	0.3249	benign	-0.439	Destabilizing	0.836	D	0.466	neutral	None	None	None	None	N
T/D	0.3348	likely_benign	0.3553	ambiguous	0.213	Stabilizing	0.593	D	0.455	neutral	None	None	None	None	N
T/E	0.2518	likely_benign	0.252	benign	0.201	Stabilizing	0.418	N	0.445	neutral	None	None	None	None	N
T/F	0.1687	likely_benign	0.1794	benign	-0.857	Destabilizing	0.002	N	0.351	neutral	None	None	None	None	N
T/G	0.2598	likely_benign	0.2781	benign	-0.966	Destabilizing	0.264	N	0.507	neutral	None	None	None	None	N
T/H	0.2567	likely_benign	0.2671	benign	-1.221	Destabilizing	0.983	D	0.52	neutral	None	None	None	None	N
T/I	0.0767	likely_benign	0.0808	benign	-0.206	Destabilizing	0.001	N	0.178	neutral	None	None	None	None	N
T/K	0.2095	likely_benign	0.203	benign	-0.621	Destabilizing	0.579	D	0.445	neutral	N	0.514991071	None	None	N
T/L	0.0622	likely_benign	0.0639	benign	-0.206	Destabilizing	0.061	N	0.321	neutral	None	None	None	None	N
T/M	0.0707	likely_benign	0.0729	benign	-0.075	Destabilizing	0.914	D	0.476	neutral	N	0.501977067	None	None	N
T/N	0.1099	likely_benign	0.1153	benign	-0.476	Destabilizing	0.836	D	0.399	neutral	None	None	None	None	N
T/P	0.0804	likely_benign	0.0849	benign	-0.349	Destabilizing	0.794	D	0.472	neutral	N	0.485689672	None	None	N
T/Q	0.2028	likely_benign	0.2018	benign	-0.602	Destabilizing	0.836	D	0.487	neutral	None	None	None	None	N
T/R	0.2004	likely_benign	0.1965	benign	-0.442	Destabilizing	0.828	D	0.489	neutral	D	0.529576522	None	None	N
T/S	0.0991	likely_benign	0.1026	benign	-0.779	Destabilizing	0.101	N	0.283	neutral	N	0.484313658	None	None	N
T/V	0.0632	likely_benign	0.0676	benign	-0.349	Destabilizing	0.001	N	0.105	neutral	None	None	None	None	N
T/W	0.5754	likely_pathogenic	0.593	pathogenic	-0.804	Destabilizing	0.983	D	0.535	neutral	None	None	None	None	N
T/Y	0.229	likely_benign	0.2413	benign	-0.569	Destabilizing	0.557	D	0.525	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.