TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28900	86923;86924;86925	chr2:178559434;178559433;178559432	chr2:179424161;179424160;179424159
N2AB	27259	82000;82001;82002	chr2:178559434;178559433;178559432	chr2:179424161;179424160;179424159
N2A	26332	79219;79220;79221	chr2:178559434;178559433;178559432	chr2:179424161;179424160;179424159
N2B	19835	59728;59729;59730	chr2:178559434;178559433;178559432	chr2:179424161;179424160;179424159
Novex-1	19960	60103;60104;60105	chr2:178559434;178559433;178559432	chr2:179424161;179424160;179424159
Novex-2	20027	60304;60305;60306	chr2:178559434;178559433;178559432	chr2:179424161;179424160;179424159
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-98
• Domain position: 56
• Structural Position: 83
• Q(SASA): 0.9164
• 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
N/K	rs727504793	0.452	None	N	0.101	0.146	0.0884992946249	gnomAD-4.0.0	2.05275E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69857E-06	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
N/A	0.1545	likely_benign	0.1403	benign	-0.276	Destabilizing	0.007	N	0.179	neutral	None	None	None	None	N
N/C	0.1492	likely_benign	0.1525	benign	0.381	Stabilizing	0.676	D	0.223	neutral	None	None	None	None	N
N/D	0.1932	likely_benign	0.1959	benign	0.05	Stabilizing	0.012	N	0.13	neutral	N	0.44938965	None	None	N
N/E	0.3859	ambiguous	0.3774	ambiguous	None	Stabilizing	0.016	N	0.106	neutral	None	None	None	None	N
N/F	0.3437	ambiguous	0.3304	benign	-0.699	Destabilizing	0.214	N	0.31	neutral	None	None	None	None	N
N/G	0.1735	likely_benign	0.1555	benign	-0.425	Destabilizing	None	N	0.105	neutral	None	None	None	None	N
N/H	0.0715	likely_benign	0.067	benign	-0.473	Destabilizing	None	N	0.095	neutral	N	0.433902909	None	None	N
N/I	0.1334	likely_benign	0.1353	benign	0.027	Stabilizing	0.055	N	0.362	neutral	N	0.485139806	None	None	N
N/K	0.2731	likely_benign	0.2805	benign	0.07	Stabilizing	None	N	0.101	neutral	N	0.429766526	None	None	N
N/L	0.1404	likely_benign	0.1433	benign	0.027	Stabilizing	0.031	N	0.274	neutral	None	None	None	None	N
N/M	0.2482	likely_benign	0.2445	benign	0.343	Stabilizing	0.628	D	0.235	neutral	None	None	None	None	N
N/P	0.1726	likely_benign	0.1651	benign	-0.048	Destabilizing	None	N	0.131	neutral	None	None	None	None	N
N/Q	0.2261	likely_benign	0.2148	benign	-0.281	Destabilizing	0.072	N	0.145	neutral	None	None	None	None	N
N/R	0.2826	likely_benign	0.2772	benign	0.146	Stabilizing	0.016	N	0.112	neutral	None	None	None	None	N
N/S	0.0635	likely_benign	0.0619	benign	-0.038	Destabilizing	None	N	0.094	neutral	N	0.433073403	None	None	N
N/T	0.0912	likely_benign	0.0887	benign	0.04	Stabilizing	0.012	N	0.121	neutral	N	0.427280794	None	None	N
N/V	0.1478	likely_benign	0.15	benign	-0.048	Destabilizing	0.072	N	0.3	neutral	None	None	None	None	N
N/W	0.6215	likely_pathogenic	0.6022	pathogenic	-0.727	Destabilizing	0.864	D	0.233	neutral	None	None	None	None	N
N/Y	0.1145	likely_benign	0.1177	benign	-0.457	Destabilizing	0.029	N	0.343	neutral	D	0.522580687	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.