TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22705	68338;68339;68340	chr2:178578917;178578916;178578915	chr2:179443644;179443643;179443642
N2AB	21064	63415;63416;63417	chr2:178578917;178578916;178578915	chr2:179443644;179443643;179443642
N2A	20137	60634;60635;60636	chr2:178578917;178578916;178578915	chr2:179443644;179443643;179443642
N2B	13640	41143;41144;41145	chr2:178578917;178578916;178578915	chr2:179443644;179443643;179443642
Novex-1	13765	41518;41519;41520	chr2:178578917;178578916;178578915	chr2:179443644;179443643;179443642
Novex-2	13832	41719;41720;41721	chr2:178578917;178578916;178578915	chr2:179443644;179443643;179443642
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-52
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1214
• 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/I	rs1461683344	-0.285	0.997	N	0.54	0.236	0.647883942074	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/I	rs1461683344	-0.285	0.997	N	0.54	0.236	0.647883942074	gnomAD-4.0.0	6.36898E-06	None	None	None	None	N	None	1.69914E-04	0	None	0	0	None	0	0	0	1.43291E-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
V/A	0.6424	likely_pathogenic	0.5916	pathogenic	-1.956	Destabilizing	0.999	D	0.648	neutral	N	0.47553043	None	None	N
V/C	0.8917	likely_pathogenic	0.8892	pathogenic	-1.456	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
V/D	0.9895	likely_pathogenic	0.9901	pathogenic	-2.341	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/E	0.9658	likely_pathogenic	0.9685	pathogenic	-2.106	Highly Destabilizing	1.0	D	0.815	deleterious	D	0.537845366	None	None	N
V/F	0.6352	likely_pathogenic	0.5617	ambiguous	-1.143	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
V/G	0.8414	likely_pathogenic	0.8388	pathogenic	-2.512	Highly Destabilizing	1.0	D	0.834	deleterious	D	0.52648906	None	None	N
V/H	0.9882	likely_pathogenic	0.9876	pathogenic	-2.211	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/I	0.089	likely_benign	0.0817	benign	-0.402	Destabilizing	0.997	D	0.54	neutral	N	0.505688437	None	None	N
V/K	0.9798	likely_pathogenic	0.9828	pathogenic	-1.651	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
V/L	0.4575	ambiguous	0.4391	ambiguous	-0.402	Destabilizing	0.997	D	0.658	neutral	N	0.521615107	None	None	N
V/M	0.4269	ambiguous	0.3927	ambiguous	-0.428	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
V/N	0.9633	likely_pathogenic	0.9648	pathogenic	-1.97	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/P	0.9763	likely_pathogenic	0.9751	pathogenic	-0.892	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
V/Q	0.9631	likely_pathogenic	0.9649	pathogenic	-1.778	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/R	0.9722	likely_pathogenic	0.9754	pathogenic	-1.559	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/S	0.8955	likely_pathogenic	0.8899	pathogenic	-2.624	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/T	0.8136	likely_pathogenic	0.8105	pathogenic	-2.227	Highly Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
V/W	0.9908	likely_pathogenic	0.9883	pathogenic	-1.621	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/Y	0.9537	likely_pathogenic	0.9447	pathogenic	-1.214	Destabilizing	1.0	D	0.786	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.