TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32059	96400;96401;96402	chr2:178543969;178543968;178543967	chr2:179408696;179408695;179408694
N2AB	30418	91477;91478;91479	chr2:178543969;178543968;178543967	chr2:179408696;179408695;179408694
N2A	29491	88696;88697;88698	chr2:178543969;178543968;178543967	chr2:179408696;179408695;179408694
N2B	22994	69205;69206;69207	chr2:178543969;178543968;178543967	chr2:179408696;179408695;179408694
Novex-1	23119	69580;69581;69582	chr2:178543969;178543968;178543967	chr2:179408696;179408695;179408694
Novex-2	23186	69781;69782;69783	chr2:178543969;178543968;178543967	chr2:179408696;179408695;179408694
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: Ig-153
• Domain position: 43
• Structural Position: 121
• Q(SASA): 0.2522
• 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/E	rs769741768	-0.674	0.984	D	0.607	0.376	0.603512723014	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
A/E	rs769741768	-0.674	0.984	D	0.607	0.376	0.603512723014	gnomAD-4.0.0	4.77427E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71742E-06	0	3.02517E-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
A/C	0.5762	likely_pathogenic	0.5498	ambiguous	-0.914	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	N
A/D	0.9735	likely_pathogenic	0.9711	pathogenic	-0.808	Destabilizing	0.988	D	0.646	neutral	None	None	None	None	N
A/E	0.9689	likely_pathogenic	0.9661	pathogenic	-0.798	Destabilizing	0.984	D	0.607	neutral	D	0.532366111	None	None	N
A/F	0.9032	likely_pathogenic	0.8869	pathogenic	-0.676	Destabilizing	0.996	D	0.723	prob.delet.	None	None	None	None	N
A/G	0.1429	likely_benign	0.1267	benign	-0.946	Destabilizing	0.004	N	0.231	neutral	N	0.471779012	None	None	N
A/H	0.9711	likely_pathogenic	0.9686	pathogenic	-1.189	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
A/I	0.8197	likely_pathogenic	0.7912	pathogenic	0.001	Stabilizing	0.996	D	0.649	neutral	None	None	None	None	N
A/K	0.9883	likely_pathogenic	0.9871	pathogenic	-1.076	Destabilizing	0.988	D	0.613	neutral	None	None	None	None	N
A/L	0.7717	likely_pathogenic	0.746	pathogenic	0.001	Stabilizing	0.959	D	0.555	neutral	None	None	None	None	N
A/M	0.8009	likely_pathogenic	0.7794	pathogenic	-0.163	Destabilizing	0.999	D	0.629	neutral	None	None	None	None	N
A/N	0.9283	likely_pathogenic	0.9206	pathogenic	-0.934	Destabilizing	0.976	D	0.671	neutral	None	None	None	None	N
A/P	0.9772	likely_pathogenic	0.974	pathogenic	-0.172	Destabilizing	0.995	D	0.639	neutral	N	0.497088768	None	None	N
A/Q	0.9563	likely_pathogenic	0.9537	pathogenic	-0.974	Destabilizing	0.996	D	0.657	neutral	None	None	None	None	N
A/R	0.9742	likely_pathogenic	0.9716	pathogenic	-0.883	Destabilizing	0.988	D	0.649	neutral	None	None	None	None	N
A/S	0.2175	likely_benign	0.2123	benign	-1.325	Destabilizing	0.896	D	0.503	neutral	D	0.531846036	None	None	N
A/T	0.3966	ambiguous	0.4071	ambiguous	-1.199	Destabilizing	0.946	D	0.457	neutral	N	0.516857941	None	None	N
A/V	0.4974	ambiguous	0.4669	ambiguous	-0.172	Destabilizing	0.946	D	0.467	neutral	N	0.466754407	None	None	N
A/W	0.9844	likely_pathogenic	0.9813	pathogenic	-1.105	Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
A/Y	0.9372	likely_pathogenic	0.9269	pathogenic	-0.634	Destabilizing	0.996	D	0.715	prob.delet.	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.