TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1105	3538;3539;3540	chr2:178782279;178782278;178782277	chr2:179647006;179647005;179647004
N2AB	1105	3538;3539;3540	chr2:178782279;178782278;178782277	chr2:179647006;179647005;179647004
N2A	1105	3538;3539;3540	chr2:178782279;178782278;178782277	chr2:179647006;179647005;179647004
N2B	1059	3400;3401;3402	chr2:178782279;178782278;178782277	chr2:179647006;179647005;179647004
Novex-1	1059	3400;3401;3402	chr2:178782279;178782278;178782277	chr2:179647006;179647005;179647004
Novex-2	1059	3400;3401;3402	chr2:178782279;178782278;178782277	chr2:179647006;179647005;179647004
Novex-3	1105	3538;3539;3540	chr2:178782279;178782278;178782277	chr2:179647006;179647005;179647004

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-4
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1546
• 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	rs1263142800	-2.14	0.104	N	0.665	0.364	0.514240282655	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/A	rs1263142800	-2.14	0.104	N	0.665	0.364	0.514240282655	gnomAD-4.0.0	5.47256E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.39577E-06	1.15931E-05	1.65585E-05

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	0.5925	likely_pathogenic	0.5817	pathogenic	-1.99	Destabilizing	0.104	N	0.665	neutral	N	0.514819133	None	None	N
V/C	0.9626	likely_pathogenic	0.9603	pathogenic	-1.26	Destabilizing	0.968	D	0.766	deleterious	None	None	None	None	N
V/D	0.9948	likely_pathogenic	0.9941	pathogenic	-2.809	Highly Destabilizing	0.667	D	0.858	deleterious	D	0.728906948	None	None	N
V/E	0.9835	likely_pathogenic	0.9811	pathogenic	-2.505	Highly Destabilizing	0.726	D	0.837	deleterious	None	None	None	None	N
V/F	0.6696	likely_pathogenic	0.6797	pathogenic	-1.134	Destabilizing	0.497	N	0.813	deleterious	D	0.641097719	None	None	N
V/G	0.8885	likely_pathogenic	0.8812	pathogenic	-2.59	Highly Destabilizing	0.667	D	0.852	deleterious	D	0.660213227	None	None	N
V/H	0.9952	likely_pathogenic	0.9946	pathogenic	-2.577	Highly Destabilizing	0.968	D	0.843	deleterious	None	None	None	None	N
V/I	0.0796	likely_benign	0.0842	benign	-0.263	Destabilizing	None	N	0.21	neutral	D	0.52739673	None	None	N
V/K	0.9913	likely_pathogenic	0.9895	pathogenic	-1.437	Destabilizing	0.726	D	0.839	deleterious	None	None	None	None	N
V/L	0.4807	ambiguous	0.4877	ambiguous	-0.263	Destabilizing	0.009	N	0.456	neutral	D	0.533985411	None	None	N
V/M	0.5345	ambiguous	0.5445	ambiguous	-0.402	Destabilizing	0.567	D	0.733	prob.delet.	None	None	None	None	N
V/N	0.9846	likely_pathogenic	0.9842	pathogenic	-2.03	Highly Destabilizing	0.89	D	0.857	deleterious	None	None	None	None	N
V/P	0.9857	likely_pathogenic	0.9851	pathogenic	-0.817	Destabilizing	0.89	D	0.827	deleterious	None	None	None	None	N
V/Q	0.9866	likely_pathogenic	0.9846	pathogenic	-1.696	Destabilizing	0.89	D	0.833	deleterious	None	None	None	None	N
V/R	0.9826	likely_pathogenic	0.9793	pathogenic	-1.594	Destabilizing	0.726	D	0.859	deleterious	None	None	None	None	N
V/S	0.9033	likely_pathogenic	0.8998	pathogenic	-2.568	Highly Destabilizing	0.726	D	0.818	deleterious	None	None	None	None	N
V/T	0.6677	likely_pathogenic	0.6449	pathogenic	-2.107	Highly Destabilizing	0.272	N	0.683	prob.neutral	None	None	None	None	N
V/W	0.9918	likely_pathogenic	0.9917	pathogenic	-1.754	Destabilizing	0.968	D	0.818	deleterious	None	None	None	None	N
V/Y	0.9753	likely_pathogenic	0.9743	pathogenic	-1.342	Destabilizing	0.726	D	0.791	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.