TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8341	25246;25247;25248	chr2:178717985;178717984;178717983	chr2:179582712;179582711;179582710
N2AB	8024	24295;24296;24297	chr2:178717985;178717984;178717983	chr2:179582712;179582711;179582710
N2A	7097	21514;21515;21516	chr2:178717985;178717984;178717983	chr2:179582712;179582711;179582710
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-68
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.6272
• 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
S/R	rs1221926854	0.083	0.132	N	0.379	0.306	0.0666544352282	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
S/R	rs1221926854	0.083	0.132	N	0.379	0.306	0.0666544352282	gnomAD-4.0.0	6.84318E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99638E-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
S/A	0.0907	likely_benign	0.1015	benign	-0.236	Destabilizing	0.002	N	0.341	neutral	None	None	None	None	I
S/C	0.2539	likely_benign	0.305	benign	-0.392	Destabilizing	0.001	N	0.353	neutral	N	0.501993975	None	None	I
S/D	0.3722	ambiguous	0.473	ambiguous	0.023	Stabilizing	0.051	N	0.296	neutral	None	None	None	None	I
S/E	0.4775	ambiguous	0.6007	pathogenic	-0.087	Destabilizing	0.001	N	0.104	neutral	None	None	None	None	I
S/F	0.312	likely_benign	0.4093	ambiguous	-0.949	Destabilizing	0.584	D	0.411	neutral	None	None	None	None	I
S/G	0.117	likely_benign	0.1359	benign	-0.289	Destabilizing	0.13	N	0.312	neutral	N	0.476784974	None	None	I
S/H	0.3386	likely_benign	0.4323	ambiguous	-0.667	Destabilizing	0.897	D	0.341	neutral	None	None	None	None	I
S/I	0.1285	likely_benign	0.1447	benign	-0.23	Destabilizing	0.002	N	0.305	neutral	D	0.523634771	None	None	I
S/K	0.5708	likely_pathogenic	0.7247	pathogenic	-0.43	Destabilizing	0.005	N	0.297	neutral	None	None	None	None	I
S/L	0.1197	likely_benign	0.1477	benign	-0.23	Destabilizing	0.028	N	0.393	neutral	None	None	None	None	I
S/M	0.2049	likely_benign	0.2183	benign	-0.12	Destabilizing	0.076	N	0.375	neutral	None	None	None	None	I
S/N	0.1308	likely_benign	0.1567	benign	-0.203	Destabilizing	0.019	N	0.339	neutral	D	0.529040591	None	None	I
S/P	0.3404	ambiguous	0.4333	ambiguous	-0.207	Destabilizing	0.699	D	0.365	neutral	None	None	None	None	I
S/Q	0.4611	ambiguous	0.5694	pathogenic	-0.452	Destabilizing	0.584	D	0.309	neutral	None	None	None	None	I
S/R	0.475	ambiguous	0.4693	ambiguous	-0.173	Destabilizing	0.132	N	0.379	neutral	N	0.491348995	None	None	I
S/T	0.0933	likely_benign	0.1035	benign	-0.316	Destabilizing	0.009	N	0.38	neutral	N	0.500315194	None	None	I
S/V	0.1659	likely_benign	0.1886	benign	-0.207	Destabilizing	0.011	N	0.395	neutral	None	None	None	None	I
S/W	0.4996	ambiguous	0.6149	pathogenic	-1.001	Destabilizing	0.97	D	0.424	neutral	None	None	None	None	I
S/Y	0.2809	likely_benign	0.3696	ambiguous	-0.699	Destabilizing	0.74	D	0.399	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.