TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23379	70360;70361;70362	chr2:178575997;178575996;178575995	chr2:179440724;179440723;179440722
N2AB	21738	65437;65438;65439	chr2:178575997;178575996;178575995	chr2:179440724;179440723;179440722
N2A	20811	62656;62657;62658	chr2:178575997;178575996;178575995	chr2:179440724;179440723;179440722
N2B	14314	43165;43166;43167	chr2:178575997;178575996;178575995	chr2:179440724;179440723;179440722
Novex-1	14439	43540;43541;43542	chr2:178575997;178575996;178575995	chr2:179440724;179440723;179440722
Novex-2	14506	43741;43742;43743	chr2:178575997;178575996;178575995	chr2:179440724;179440723;179440722
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-129
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1278
• 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	None	None	0.166	N	0.439	0.093	0.0986583533028	gnomAD-4.0.0	1.59481E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86689E-06	0	0
T/I	rs773975500	0.2	0.326	N	0.631	0.119	0.21279746466	gnomAD-2.1.1	2.42E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.96284E-04	None	0	0	0
T/I	rs773975500	0.2	0.326	N	0.631	0.119	0.21279746466	gnomAD-4.0.0	6.84935E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16007E-04	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	0.0986	likely_benign	0.0914	benign	-1.178	Destabilizing	0.166	N	0.439	neutral	N	0.452640694	None	None	N
T/C	0.3323	likely_benign	0.3117	benign	-0.837	Destabilizing	0.991	D	0.65	neutral	None	None	None	None	N
T/D	0.4664	ambiguous	0.449	ambiguous	-1.049	Destabilizing	0.561	D	0.652	neutral	None	None	None	None	N
T/E	0.2225	likely_benign	0.242	benign	-0.897	Destabilizing	0.39	N	0.629	neutral	None	None	None	None	N
T/F	0.2374	likely_benign	0.2258	benign	-1.012	Destabilizing	0.39	N	0.705	prob.neutral	None	None	None	None	N
T/G	0.2453	likely_benign	0.224	benign	-1.557	Destabilizing	0.561	D	0.649	neutral	None	None	None	None	N
T/H	0.2085	likely_benign	0.2043	benign	-1.748	Destabilizing	0.818	D	0.681	prob.neutral	None	None	None	None	N
T/I	0.1929	likely_benign	0.1888	benign	-0.201	Destabilizing	0.326	N	0.631	neutral	N	0.451880226	None	None	N
T/K	0.1768	likely_benign	0.1952	benign	-0.528	Destabilizing	0.004	N	0.401	neutral	None	None	None	None	N
T/L	0.1007	likely_benign	0.0992	benign	-0.201	Destabilizing	0.002	N	0.355	neutral	None	None	None	None	N
T/M	0.0757	likely_benign	0.0745	benign	-0.101	Destabilizing	0.103	N	0.51	neutral	None	None	None	None	N
T/N	0.1319	likely_benign	0.124	benign	-1.026	Destabilizing	0.491	N	0.553	neutral	N	0.453147673	None	None	N
T/P	0.8941	likely_pathogenic	0.8981	pathogenic	-0.495	Destabilizing	0.873	D	0.687	prob.neutral	N	0.479734625	None	None	N
T/Q	0.152	likely_benign	0.1507	benign	-0.931	Destabilizing	0.818	D	0.685	prob.neutral	None	None	None	None	N
T/R	0.1533	likely_benign	0.1657	benign	-0.64	Destabilizing	0.39	N	0.667	neutral	None	None	None	None	N
T/S	0.0962	likely_benign	0.0891	benign	-1.313	Destabilizing	0.016	N	0.227	neutral	N	0.44543412	None	None	N
T/V	0.1444	likely_benign	0.1426	benign	-0.495	Destabilizing	0.209	N	0.503	neutral	None	None	None	None	N
T/W	0.5853	likely_pathogenic	0.5667	pathogenic	-1.051	Destabilizing	0.972	D	0.662	neutral	None	None	None	None	N
T/Y	0.2821	likely_benign	0.2717	benign	-0.707	Destabilizing	0.017	N	0.563	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.