TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35646	107161;107162;107163	chr2:178528815;178528814;178528813	chr2:179393542;179393541;179393540
N2AB	34005	102238;102239;102240	chr2:178528815;178528814;178528813	chr2:179393542;179393541;179393540
N2A	33078	99457;99458;99459	chr2:178528815;178528814;178528813	chr2:179393542;179393541;179393540
N2B	26581	79966;79967;79968	chr2:178528815;178528814;178528813	chr2:179393542;179393541;179393540
Novex-1	26706	80341;80342;80343	chr2:178528815;178528814;178528813	chr2:179393542;179393541;179393540
Novex-2	26773	80542;80543;80544	chr2:178528815;178528814;178528813	chr2:179393542;179393541;179393540
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-167
• Domain position: 40
• Structural Position: 59
• Q(SASA): 0.5519
• 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	rs1558970634	None	None	N	0.11	0.109	0.0666544352282	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
T/A	rs1558970634	None	None	N	0.11	0.109	0.0666544352282	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8583E-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	0.0758	likely_benign	0.0759	benign	-0.612	Destabilizing	None	N	0.11	neutral	N	0.459945865	None	None	N
T/C	0.4898	ambiguous	0.4403	ambiguous	-0.465	Destabilizing	0.356	N	0.341	neutral	None	None	None	None	N
T/D	0.3179	likely_benign	0.3193	benign	0.46	Stabilizing	0.038	N	0.346	neutral	None	None	None	None	N
T/E	0.2314	likely_benign	0.2426	benign	0.442	Stabilizing	0.016	N	0.341	neutral	None	None	None	None	N
T/F	0.2699	likely_benign	0.2846	benign	-1.056	Destabilizing	0.356	N	0.372	neutral	None	None	None	None	N
T/G	0.2247	likely_benign	0.2048	benign	-0.775	Destabilizing	0.016	N	0.313	neutral	None	None	None	None	N
T/H	0.2505	likely_benign	0.2399	benign	-0.83	Destabilizing	0.356	N	0.367	neutral	None	None	None	None	N
T/I	0.1747	likely_benign	0.1889	benign	-0.284	Destabilizing	0.055	N	0.394	neutral	N	0.461332732	None	None	N
T/K	0.1393	likely_benign	0.1461	benign	-0.241	Destabilizing	0.016	N	0.365	neutral	None	None	None	None	N
T/L	0.1106	likely_benign	0.1117	benign	-0.284	Destabilizing	0.016	N	0.345	neutral	None	None	None	None	N
T/M	0.1256	likely_benign	0.1244	benign	-0.357	Destabilizing	0.356	N	0.338	neutral	None	None	None	None	N
T/N	0.1236	likely_benign	0.1221	benign	-0.231	Destabilizing	0.029	N	0.183	neutral	N	0.459079074	None	None	N
T/P	0.0818	likely_benign	0.0892	benign	-0.365	Destabilizing	None	N	0.203	neutral	N	0.460986015	None	None	N
T/Q	0.1845	likely_benign	0.1792	benign	-0.296	Destabilizing	0.072	N	0.396	neutral	None	None	None	None	N
T/R	0.1279	likely_benign	0.1319	benign	-0.031	Destabilizing	None	N	0.217	neutral	None	None	None	None	N
T/S	0.1099	likely_benign	0.1048	benign	-0.526	Destabilizing	None	N	0.113	neutral	N	0.42198491	None	None	N
T/V	0.15	likely_benign	0.1511	benign	-0.365	Destabilizing	0.016	N	0.193	neutral	None	None	None	None	N
T/W	0.5959	likely_pathogenic	0.5781	pathogenic	-1.077	Destabilizing	0.864	D	0.38	neutral	None	None	None	None	N
T/Y	0.3204	likely_benign	0.3091	benign	-0.772	Destabilizing	0.356	N	0.369	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.