TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14183	42772;42773;42774	chr2:178633952;178633951;178633950	chr2:179498679;179498678;179498677
N2AB	12542	37849;37850;37851	chr2:178633952;178633951;178633950	chr2:179498679;179498678;179498677
N2A	11615	35068;35069;35070	chr2:178633952;178633951;178633950	chr2:179498679;179498678;179498677
N2B	5118	15577;15578;15579	chr2:178633952;178633951;178633950	chr2:179498679;179498678;179498677
Novex-1	5243	15952;15953;15954	chr2:178633952;178633951;178633950	chr2:179498679;179498678;179498677
Novex-2	5310	16153;16154;16155	chr2:178633952;178633951;178633950	chr2:179498679;179498678;179498677
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-92
• Domain position: 42
• Structural Position: 70
• Q(SASA): 0.3916
• 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
T/A	rs72650081	None	0.91	N	0.358	0.17	0.276482976112	gnomAD-4.0.0	2.73737E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.5985E-06	0	0
T/K	None	None	0.98	N	0.422	0.379	0.421920138742	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/R	None	None	0.998	N	0.469	0.379	0.501122797481	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
T/A	0.0904	likely_benign	0.0937	benign	-0.28	Destabilizing	0.91	D	0.358	neutral	N	0.481265982	None	None	N
T/C	0.5166	ambiguous	0.5213	ambiguous	-0.295	Destabilizing	1.0	D	0.512	neutral	None	None	None	None	N
T/D	0.4479	ambiguous	0.4677	ambiguous	0.34	Stabilizing	0.985	D	0.42	neutral	None	None	None	None	N
T/E	0.3731	ambiguous	0.4015	ambiguous	0.27	Stabilizing	0.985	D	0.423	neutral	None	None	None	None	N
T/F	0.307	likely_benign	0.3516	ambiguous	-0.783	Destabilizing	0.999	D	0.536	neutral	None	None	None	None	N
T/G	0.2886	likely_benign	0.3275	benign	-0.406	Destabilizing	0.985	D	0.457	neutral	None	None	None	None	N
T/H	0.2802	likely_benign	0.2931	benign	-0.656	Destabilizing	1.0	D	0.535	neutral	None	None	None	None	N
T/I	0.2299	likely_benign	0.2372	benign	-0.07	Destabilizing	0.998	D	0.467	neutral	N	0.512916716	None	None	N
T/K	0.2395	likely_benign	0.2705	benign	-0.298	Destabilizing	0.98	D	0.422	neutral	N	0.49726295	None	None	N
T/L	0.1248	likely_benign	0.1294	benign	-0.07	Destabilizing	0.985	D	0.385	neutral	None	None	None	None	N
T/M	0.1375	likely_benign	0.1381	benign	-0.058	Destabilizing	1.0	D	0.487	neutral	None	None	None	None	N
T/N	0.1289	likely_benign	0.1194	benign	-0.119	Destabilizing	0.999	D	0.397	neutral	None	None	None	None	N
T/P	0.0837	likely_benign	0.0889	benign	-0.111	Destabilizing	0.011	N	0.197	neutral	N	0.387402184	None	None	N
T/Q	0.2611	likely_benign	0.2777	benign	-0.293	Destabilizing	0.999	D	0.478	neutral	None	None	None	None	N
T/R	0.1926	likely_benign	0.2123	benign	-0.066	Destabilizing	0.998	D	0.469	neutral	N	0.502781422	None	None	N
T/S	0.1273	likely_benign	0.1317	benign	-0.33	Destabilizing	0.98	D	0.407	neutral	N	0.484712314	None	None	N
T/V	0.1765	likely_benign	0.1835	benign	-0.111	Destabilizing	0.985	D	0.348	neutral	None	None	None	None	N
T/W	0.7015	likely_pathogenic	0.7423	pathogenic	-0.824	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	N
T/Y	0.3196	likely_benign	0.3559	ambiguous	-0.52	Destabilizing	0.999	D	0.535	neutral	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.