TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24803	74632;74633;74634	chr2:178571725;178571724;178571723	chr2:179436452;179436451;179436450
N2AB	23162	69709;69710;69711	chr2:178571725;178571724;178571723	chr2:179436452;179436451;179436450
N2A	22235	66928;66929;66930	chr2:178571725;178571724;178571723	chr2:179436452;179436451;179436450
N2B	15738	47437;47438;47439	chr2:178571725;178571724;178571723	chr2:179436452;179436451;179436450
Novex-1	15863	47812;47813;47814	chr2:178571725;178571724;178571723	chr2:179436452;179436451;179436450
Novex-2	15930	48013;48014;48015	chr2:178571725;178571724;178571723	chr2:179436452;179436451;179436450
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-133
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.1156
• 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
V/A	None	None	0.104	N	0.665	0.37	0.546131560702	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
V/I	None	None	None	N	0.211	0.033	0.241664281697	gnomAD-4.0.0	1.59193E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85954E-06	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
V/A	0.8806	likely_pathogenic	0.8835	pathogenic	-2.079	Highly Destabilizing	0.104	N	0.665	neutral	N	0.488224683	None	None	N
V/C	0.9159	likely_pathogenic	0.912	pathogenic	-1.617	Destabilizing	0.968	D	0.753	deleterious	None	None	None	None	N
V/D	0.9904	likely_pathogenic	0.9906	pathogenic	-2.813	Highly Destabilizing	0.667	D	0.859	deleterious	D	0.522965163	None	None	N
V/E	0.9837	likely_pathogenic	0.9852	pathogenic	-2.567	Highly Destabilizing	0.726	D	0.83	deleterious	None	None	None	None	N
V/F	0.4273	ambiguous	0.4242	ambiguous	-1.169	Destabilizing	0.497	N	0.787	deleterious	N	0.50359346	None	None	N
V/G	0.9257	likely_pathogenic	0.9301	pathogenic	-2.641	Highly Destabilizing	0.667	D	0.858	deleterious	D	0.522965163	None	None	N
V/H	0.9872	likely_pathogenic	0.9875	pathogenic	-2.471	Highly Destabilizing	0.968	D	0.839	deleterious	None	None	None	None	N
V/I	0.0554	likely_benign	0.0532	benign	-0.492	Destabilizing	None	N	0.211	neutral	N	0.462849232	None	None	N
V/K	0.9827	likely_pathogenic	0.9838	pathogenic	-1.638	Destabilizing	0.726	D	0.83	deleterious	None	None	None	None	N
V/L	0.272	likely_benign	0.2592	benign	-0.492	Destabilizing	0.009	N	0.473	neutral	N	0.474836228	None	None	N
V/M	0.3636	ambiguous	0.3518	ambiguous	-0.633	Destabilizing	0.567	D	0.701	prob.neutral	None	None	None	None	N
V/N	0.9656	likely_pathogenic	0.9645	pathogenic	-2.053	Highly Destabilizing	0.89	D	0.837	deleterious	None	None	None	None	N
V/P	0.9791	likely_pathogenic	0.9794	pathogenic	-0.996	Destabilizing	0.89	D	0.812	deleterious	None	None	None	None	N
V/Q	0.9797	likely_pathogenic	0.981	pathogenic	-1.837	Destabilizing	0.89	D	0.826	deleterious	None	None	None	None	N
V/R	0.9715	likely_pathogenic	0.9743	pathogenic	-1.567	Destabilizing	0.726	D	0.84	deleterious	None	None	None	None	N
V/S	0.9505	likely_pathogenic	0.9519	pathogenic	-2.654	Highly Destabilizing	0.726	D	0.821	deleterious	None	None	None	None	N
V/T	0.9065	likely_pathogenic	0.9058	pathogenic	-2.262	Highly Destabilizing	0.272	N	0.684	prob.neutral	None	None	None	None	N
V/W	0.9777	likely_pathogenic	0.9775	pathogenic	-1.755	Destabilizing	0.968	D	0.829	deleterious	None	None	None	None	N
V/Y	0.9142	likely_pathogenic	0.9157	pathogenic	-1.367	Destabilizing	0.726	D	0.763	deleterious	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.