TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14280	43063;43064;43065	chr2:178633521;178633520;178633519	chr2:179498248;179498247;179498246
N2AB	12639	38140;38141;38142	chr2:178633521;178633520;178633519	chr2:179498248;179498247;179498246
N2A	11712	35359;35360;35361	chr2:178633521;178633520;178633519	chr2:179498248;179498247;179498246
N2B	5215	15868;15869;15870	chr2:178633521;178633520;178633519	chr2:179498248;179498247;179498246
Novex-1	5340	16243;16244;16245	chr2:178633521;178633520;178633519	chr2:179498248;179498247;179498246
Novex-2	5407	16444;16445;16446	chr2:178633521;178633520;178633519	chr2:179498248;179498247;179498246
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-93
• Domain position: 50
• Structural Position: 130
• Q(SASA): 0.5802
• 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
D/E	rs760643071	0.046	0.014	N	0.183	0.098	0.0762999501168	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.35E-05	0
D/E	rs760643071	0.046	0.014	N	0.183	0.098	0.0762999501168	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
D/E	rs760643071	0.046	0.014	N	0.183	0.098	0.0762999501168	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85948E-06	0	0
D/G	rs181902304	-0.409	0.698	D	0.371	0.424	None	gnomAD-2.1.1	9.29E-05	None	None	None	None	N	None	4.13E-05	2.83094E-04	None	0	0	None	3.27E-05	None	0	1.09539E-04	0
D/G	rs181902304	-0.409	0.698	D	0.371	0.424	None	gnomAD-3.1.2	7.23E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47059E-04	0	0
D/G	rs181902304	-0.409	0.698	D	0.371	0.424	None	gnomAD-4.0.0	5.45471E-05	None	None	None	None	N	None	1.33522E-05	1.66789E-04	None	0	0	None	0	0	6.27327E-05	2.19587E-05	1.60174E-05
D/V	rs181902304	0.315	0.89	D	0.617	0.46	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93199E-04	None	0	0	0	0	0
D/V	rs181902304	0.315	0.89	D	0.617	0.46	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
D/V	rs181902304	0.315	0.89	D	0.617	0.46	None	gnomAD-4.0.0	6.56892E-06	None	None	None	None	N	None	0	0	None	0	1.93648E-04	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
D/A	0.1903	likely_benign	0.2334	benign	-0.098	Destabilizing	0.014	N	0.307	neutral	D	0.60522681	None	None	N
D/C	0.702	likely_pathogenic	0.779	pathogenic	0.112	Stabilizing	0.994	D	0.643	neutral	None	None	None	None	N
D/E	0.1473	likely_benign	0.175	benign	-0.243	Destabilizing	0.014	N	0.183	neutral	N	0.497609114	None	None	N
D/F	0.6344	likely_pathogenic	0.6808	pathogenic	-0.113	Destabilizing	0.978	D	0.639	neutral	None	None	None	None	N
D/G	0.2642	likely_benign	0.2926	benign	-0.261	Destabilizing	0.698	D	0.371	neutral	D	0.58949267	None	None	N
D/H	0.3352	likely_benign	0.4578	ambiguous	0.185	Stabilizing	0.992	D	0.471	neutral	D	0.658616143	None	None	N
D/I	0.3604	ambiguous	0.4473	ambiguous	0.272	Stabilizing	0.956	D	0.643	neutral	None	None	None	None	N
D/K	0.3802	ambiguous	0.5245	ambiguous	0.527	Stabilizing	0.754	D	0.371	neutral	None	None	None	None	N
D/L	0.4394	ambiguous	0.5346	ambiguous	0.272	Stabilizing	0.915	D	0.649	neutral	None	None	None	None	N
D/M	0.6449	likely_pathogenic	0.7105	pathogenic	0.305	Stabilizing	0.998	D	0.647	neutral	None	None	None	None	N
D/N	0.1225	likely_benign	0.1172	benign	0.228	Stabilizing	0.942	D	0.375	neutral	D	0.535932515	None	None	N
D/P	0.8814	likely_pathogenic	0.9183	pathogenic	0.17	Stabilizing	0.978	D	0.461	neutral	None	None	None	None	N
D/Q	0.3484	ambiguous	0.4717	ambiguous	0.249	Stabilizing	0.915	D	0.379	neutral	None	None	None	None	N
D/R	0.4253	ambiguous	0.5965	pathogenic	0.666	Stabilizing	0.956	D	0.599	neutral	None	None	None	None	N
D/S	0.1461	likely_benign	0.1563	benign	0.145	Stabilizing	0.754	D	0.311	neutral	None	None	None	None	N
D/T	0.2654	likely_benign	0.3014	benign	0.276	Stabilizing	0.956	D	0.396	neutral	None	None	None	None	N
D/V	0.2078	likely_benign	0.2663	benign	0.17	Stabilizing	0.89	D	0.617	neutral	D	0.60378267	None	None	N
D/W	0.8787	likely_pathogenic	0.9261	pathogenic	-0.023	Destabilizing	0.998	D	0.647	neutral	None	None	None	None	N
D/Y	0.2637	likely_benign	0.3272	benign	0.126	Stabilizing	0.997	D	0.636	neutral	D	0.770873016	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.