TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18520	55783;55784;55785	chr2:178601439;178601438;178601437	chr2:179466166;179466165;179466164
N2AB	16879	50860;50861;50862	chr2:178601439;178601438;178601437	chr2:179466166;179466165;179466164
N2A	15952	48079;48080;48081	chr2:178601439;178601438;178601437	chr2:179466166;179466165;179466164
N2B	9455	28588;28589;28590	chr2:178601439;178601438;178601437	chr2:179466166;179466165;179466164
Novex-1	9580	28963;28964;28965	chr2:178601439;178601438;178601437	chr2:179466166;179466165;179466164
Novex-2	9647	29164;29165;29166	chr2:178601439;178601438;178601437	chr2:179466166;179466165;179466164
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-22
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2994
• 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	0.01	N	0.08	0.112	0.170165803431	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	7.32654E-05
T/I	None	None	0.784	N	0.468	0.219	0.327419511103	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	0.1084	likely_benign	0.1234	benign	-1.211	Destabilizing	0.01	N	0.08	neutral	N	0.471111716	None	None	N
T/C	0.4147	ambiguous	0.4714	ambiguous	-0.778	Destabilizing	0.007	N	0.211	neutral	None	None	None	None	N
T/D	0.438	ambiguous	0.5162	ambiguous	-0.553	Destabilizing	0.543	D	0.437	neutral	None	None	None	None	N
T/E	0.4411	ambiguous	0.5032	ambiguous	-0.457	Destabilizing	0.704	D	0.432	neutral	None	None	None	None	N
T/F	0.4522	ambiguous	0.5232	ambiguous	-0.996	Destabilizing	0.981	D	0.513	neutral	None	None	None	None	N
T/G	0.2187	likely_benign	0.2596	benign	-1.557	Destabilizing	0.329	N	0.451	neutral	None	None	None	None	N
T/H	0.356	ambiguous	0.417	ambiguous	-1.628	Destabilizing	0.944	D	0.5	neutral	None	None	None	None	N
T/I	0.3772	ambiguous	0.4333	ambiguous	-0.343	Destabilizing	0.784	D	0.468	neutral	N	0.514979924	None	None	N
T/K	0.3427	ambiguous	0.431	ambiguous	-0.663	Destabilizing	0.704	D	0.436	neutral	None	None	None	None	N
T/L	0.156	likely_benign	0.1784	benign	-0.343	Destabilizing	0.495	N	0.449	neutral	None	None	None	None	N
T/M	0.1173	likely_benign	0.1351	benign	-0.151	Destabilizing	0.981	D	0.465	neutral	None	None	None	None	N
T/N	0.0988	likely_benign	0.1182	benign	-0.884	Destabilizing	0.006	N	0.2	neutral	N	0.501914626	None	None	N
T/P	0.1428	likely_benign	0.1814	benign	-0.6	Destabilizing	0.006	N	0.265	neutral	N	0.485809023	None	None	N
T/Q	0.2798	likely_benign	0.333	benign	-0.915	Destabilizing	0.944	D	0.478	neutral	None	None	None	None	N
T/R	0.3139	likely_benign	0.4158	ambiguous	-0.571	Destabilizing	0.893	D	0.491	neutral	None	None	None	None	N
T/S	0.1135	likely_benign	0.1307	benign	-1.26	Destabilizing	0.065	N	0.105	neutral	N	0.462433518	None	None	N
T/V	0.2545	likely_benign	0.2807	benign	-0.6	Destabilizing	0.704	D	0.329	neutral	None	None	None	None	N
T/W	0.768	likely_pathogenic	0.8326	pathogenic	-0.915	Destabilizing	0.995	D	0.538	neutral	None	None	None	None	N
T/Y	0.47	ambiguous	0.5522	ambiguous	-0.663	Destabilizing	0.981	D	0.509	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.