TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23425	70498;70499;70500	chr2:178575859;178575858;178575857	chr2:179440586;179440585;179440584
N2AB	21784	65575;65576;65577	chr2:178575859;178575858;178575857	chr2:179440586;179440585;179440584
N2A	20857	62794;62795;62796	chr2:178575859;178575858;178575857	chr2:179440586;179440585;179440584
N2B	14360	43303;43304;43305	chr2:178575859;178575858;178575857	chr2:179440586;179440585;179440584
Novex-1	14485	43678;43679;43680	chr2:178575859;178575858;178575857	chr2:179440586;179440585;179440584
Novex-2	14552	43879;43880;43881	chr2:178575859;178575858;178575857	chr2:179440586;179440585;179440584
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-129
• Domain position: 81
• Structural Position: 168
• Q(SASA): 0.6769
• 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
S/C	rs566232507	-0.115	0.994	N	0.414	0.423	0.498001352042	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
S/C	rs566232507	-0.115	0.994	N	0.414	0.423	0.498001352042	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
S/C	rs566232507	-0.115	0.994	N	0.414	0.423	0.498001352042	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
S/C	rs566232507	-0.115	0.994	N	0.414	0.423	0.498001352042	gnomAD-4.0.0	3.84388E-06	None	None	None	None	N	None	0	5.08251E-05	None	0	0	None	0	0	0	0	0
S/I	rs980974415	None	0.884	N	0.432	0.442	0.642832020782	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/I	rs980974415	None	0.884	N	0.432	0.442	0.642832020782	gnomAD-4.0.0	6.57523E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47067E-05	0	0
S/N	None	None	0.684	N	0.384	0.151	0.208000267992	gnomAD-4.0.0	1.59167E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85933E-06	0	0
S/T	rs980974415	None	0.001	N	0.128	0.068	0.137902524267	gnomAD-4.0.0	1.11417E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7156E-05	0	3.0248E-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
S/A	0.0985	likely_benign	0.1056	benign	-0.286	Destabilizing	0.016	N	0.144	neutral	None	None	None	None	N
S/C	0.1548	likely_benign	0.1637	benign	-0.243	Destabilizing	0.994	D	0.414	neutral	N	0.489001374	None	None	N
S/D	0.5136	ambiguous	0.5585	ambiguous	0.157	Stabilizing	0.742	D	0.33	neutral	None	None	None	None	N
S/E	0.474	ambiguous	0.5226	ambiguous	0.082	Stabilizing	0.742	D	0.317	neutral	None	None	None	None	N
S/F	0.316	likely_benign	0.3284	benign	-0.759	Destabilizing	0.953	D	0.468	neutral	None	None	None	None	N
S/G	0.1768	likely_benign	0.1799	benign	-0.434	Destabilizing	0.472	N	0.353	neutral	N	0.49959721	None	None	N
S/H	0.4328	ambiguous	0.4558	ambiguous	-0.891	Destabilizing	0.996	D	0.414	neutral	None	None	None	None	N
S/I	0.2459	likely_benign	0.267	benign	-0.028	Destabilizing	0.884	D	0.432	neutral	N	0.511371589	None	None	N
S/K	0.7377	likely_pathogenic	0.7857	pathogenic	-0.526	Destabilizing	0.742	D	0.313	neutral	None	None	None	None	N
S/L	0.1459	likely_benign	0.1551	benign	-0.028	Destabilizing	0.59	D	0.395	neutral	None	None	None	None	N
S/M	0.1722	likely_benign	0.1819	benign	0.085	Stabilizing	0.984	D	0.419	neutral	None	None	None	None	N
S/N	0.1785	likely_benign	0.1851	benign	-0.241	Destabilizing	0.684	D	0.384	neutral	N	0.521381113	None	None	N
S/P	0.8572	likely_pathogenic	0.8531	pathogenic	-0.083	Destabilizing	0.953	D	0.423	neutral	None	None	None	None	N
S/Q	0.4906	ambiguous	0.5211	ambiguous	-0.44	Destabilizing	0.953	D	0.41	neutral	None	None	None	None	N
S/R	0.7162	likely_pathogenic	0.7612	pathogenic	-0.326	Destabilizing	0.884	D	0.439	neutral	N	0.513396348	None	None	N
S/T	0.0654	likely_benign	0.0669	benign	-0.316	Destabilizing	0.001	N	0.128	neutral	N	0.448688722	None	None	N
S/V	0.2107	likely_benign	0.2344	benign	-0.083	Destabilizing	0.59	D	0.391	neutral	None	None	None	None	N
S/W	0.5387	ambiguous	0.5462	ambiguous	-0.8	Destabilizing	0.996	D	0.537	neutral	None	None	None	None	N
S/Y	0.2914	likely_benign	0.2962	benign	-0.515	Destabilizing	0.984	D	0.463	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.