TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21251	63976;63977;63978	chr2:178587558;178587557;178587556	chr2:179452285;179452284;179452283
N2AB	19610	59053;59054;59055	chr2:178587558;178587557;178587556	chr2:179452285;179452284;179452283
N2A	18683	56272;56273;56274	chr2:178587558;178587557;178587556	chr2:179452285;179452284;179452283
N2B	12186	36781;36782;36783	chr2:178587558;178587557;178587556	chr2:179452285;179452284;179452283
Novex-1	12311	37156;37157;37158	chr2:178587558;178587557;178587556	chr2:179452285;179452284;179452283
Novex-2	12378	37357;37358;37359	chr2:178587558;178587557;178587556	chr2:179452285;179452284;179452283
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-123
• Domain position: 75
• Structural Position: 162
• Q(SASA): 0.7175
• Predicted PPI site: I

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
P/A	None	None	0.001	N	0.134	0.146	0.195762928549	gnomAD-4.0.0	6.85253E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00383E-07	0	0
P/S	None	None	0.003	N	0.133	0.129	0.165133752707	gnomAD-4.0.0	4.11152E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.4023E-06	0	0
P/T	None	None	0.002	N	0.172	0.18	0.243398259712	gnomAD-4.0.0	6.85253E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00383E-07	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
P/A	0.0756	likely_benign	0.0757	benign	-0.288	Destabilizing	0.001	N	0.134	neutral	N	0.448920795	None	None	I
P/C	0.5223	ambiguous	0.5042	ambiguous	-0.649	Destabilizing	0.983	D	0.324	neutral	None	None	None	None	I
P/D	0.3448	ambiguous	0.3176	benign	-0.31	Destabilizing	0.418	N	0.291	neutral	None	None	None	None	I
P/E	0.2296	likely_benign	0.2102	benign	-0.437	Destabilizing	0.418	N	0.321	neutral	None	None	None	None	I
P/F	0.5945	likely_pathogenic	0.5934	pathogenic	-0.704	Destabilizing	0.557	D	0.336	neutral	None	None	None	None	I
P/G	0.2535	likely_benign	0.2509	benign	-0.356	Destabilizing	0.129	N	0.339	neutral	None	None	None	None	I
P/H	0.235	likely_benign	0.2156	benign	-0.019	Destabilizing	0.94	D	0.34	neutral	None	None	None	None	I
P/I	0.3252	likely_benign	0.3053	benign	-0.26	Destabilizing	0.264	N	0.345	neutral	None	None	None	None	I
P/K	0.2831	likely_benign	0.2596	benign	-0.319	Destabilizing	0.418	N	0.331	neutral	None	None	None	None	I
P/L	0.1461	likely_benign	0.1405	benign	-0.26	Destabilizing	0.001	N	0.175	neutral	N	0.481398573	None	None	I
P/M	0.2995	likely_benign	0.2941	benign	-0.415	Destabilizing	0.716	D	0.341	neutral	None	None	None	None	I
P/N	0.2848	likely_benign	0.2691	benign	-0.071	Destabilizing	0.418	N	0.328	neutral	None	None	None	None	I
P/Q	0.177	likely_benign	0.1673	benign	-0.307	Destabilizing	0.794	D	0.319	neutral	N	0.487516469	None	None	I
P/R	0.2256	likely_benign	0.2034	benign	0.144	Stabilizing	0.655	D	0.366	neutral	N	0.505120794	None	None	I
P/S	0.1191	likely_benign	0.1157	benign	-0.37	Destabilizing	0.003	N	0.133	neutral	N	0.410687694	None	None	I
P/T	0.1009	likely_benign	0.0975	benign	-0.404	Destabilizing	0.002	N	0.172	neutral	N	0.479435703	None	None	I
P/V	0.1932	likely_benign	0.1871	benign	-0.239	Destabilizing	0.129	N	0.342	neutral	None	None	None	None	I
P/W	0.7218	likely_pathogenic	0.7028	pathogenic	-0.779	Destabilizing	0.983	D	0.346	neutral	None	None	None	None	I
P/Y	0.5118	ambiguous	0.4886	ambiguous	-0.479	Destabilizing	0.836	D	0.337	neutral	None	None	None	None	I

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.