TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26052	78379;78380;78381	chr2:178567978;178567977;178567976	chr2:179432705;179432704;179432703
N2AB	24411	73456;73457;73458	chr2:178567978;178567977;178567976	chr2:179432705;179432704;179432703
N2A	23484	70675;70676;70677	chr2:178567978;178567977;178567976	chr2:179432705;179432704;179432703
N2B	16987	51184;51185;51186	chr2:178567978;178567977;178567976	chr2:179432705;179432704;179432703
Novex-1	17112	51559;51560;51561	chr2:178567978;178567977;178567976	chr2:179432705;179432704;179432703
Novex-2	17179	51760;51761;51762	chr2:178567978;178567977;178567976	chr2:179432705;179432704;179432703
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-77
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1315
• 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
A/V	rs1706569332	None	None	N	0.299	0.071	0.107399877778	gnomAD-4.0.0	3.18371E-06	None	None	None	None	N	None	0	0	None	0	5.55093E-05	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
A/C	0.3215	likely_benign	0.2966	benign	-0.695	Destabilizing	0.356	N	0.673	neutral	None	None	None	None	N
A/D	0.7799	likely_pathogenic	0.7977	pathogenic	-1.958	Destabilizing	0.038	N	0.733	prob.delet.	None	None	None	None	N
A/E	0.6958	likely_pathogenic	0.7087	pathogenic	-1.692	Destabilizing	0.055	N	0.686	prob.neutral	N	0.490700807	None	None	N
A/F	0.434	ambiguous	0.4203	ambiguous	-0.423	Destabilizing	0.214	N	0.811	deleterious	None	None	None	None	N
A/G	0.2491	likely_benign	0.2428	benign	-1.273	Destabilizing	0.024	N	0.553	neutral	N	0.479091012	None	None	N
A/H	0.8215	likely_pathogenic	0.8064	pathogenic	-1.916	Destabilizing	0.356	N	0.812	deleterious	None	None	None	None	N
A/I	0.141	likely_benign	0.1435	benign	0.783	Stabilizing	0.013	N	0.685	prob.neutral	None	None	None	None	N
A/K	0.9103	likely_pathogenic	0.9103	pathogenic	-0.839	Destabilizing	0.072	N	0.686	prob.neutral	None	None	None	None	N
A/L	0.1745	likely_benign	0.1696	benign	0.783	Stabilizing	0.016	N	0.644	neutral	None	None	None	None	N
A/M	0.1999	likely_benign	0.1883	benign	0.468	Stabilizing	0.214	N	0.775	deleterious	None	None	None	None	N
A/N	0.5342	ambiguous	0.5404	ambiguous	-1.285	Destabilizing	0.001	N	0.581	neutral	None	None	None	None	N
A/P	0.7504	likely_pathogenic	0.7558	pathogenic	0.327	Stabilizing	0.106	N	0.753	deleterious	N	0.472596552	None	None	N
A/Q	0.7374	likely_pathogenic	0.7297	pathogenic	-0.947	Destabilizing	0.356	N	0.795	deleterious	None	None	None	None	N
A/R	0.8904	likely_pathogenic	0.8887	pathogenic	-1.221	Destabilizing	0.072	N	0.773	deleterious	None	None	None	None	N
A/S	0.1164	likely_benign	0.1155	benign	-1.714	Destabilizing	0.001	N	0.249	neutral	N	0.517190723	None	None	N
A/T	0.0749	likely_benign	0.0709	benign	-1.288	Destabilizing	None	N	0.255	neutral	N	0.44248232	None	None	N
A/V	0.0726	likely_benign	0.0752	benign	0.327	Stabilizing	None	N	0.299	neutral	N	0.367746914	None	None	N
A/W	0.8941	likely_pathogenic	0.885	pathogenic	-1.289	Destabilizing	0.864	D	0.813	deleterious	None	None	None	None	N
A/Y	0.656	likely_pathogenic	0.6331	pathogenic	-0.603	Destabilizing	0.356	N	0.809	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.