TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22406	67441;67442;67443	chr2:178580071;178580070;178580069	chr2:179444798;179444797;179444796
N2AB	20765	62518;62519;62520	chr2:178580071;178580070;178580069	chr2:179444798;179444797;179444796
N2A	19838	59737;59738;59739	chr2:178580071;178580070;178580069	chr2:179444798;179444797;179444796
N2B	13341	40246;40247;40248	chr2:178580071;178580070;178580069	chr2:179444798;179444797;179444796
Novex-1	13466	40621;40622;40623	chr2:178580071;178580070;178580069	chr2:179444798;179444797;179444796
Novex-2	13533	40822;40823;40824	chr2:178580071;178580070;178580069	chr2:179444798;179444797;179444796
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: Fn3-50
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.625
• 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/N	rs766588174	-0.053	0.015	N	0.213	0.145	0.201204373187	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
T/N	rs766588174	-0.053	0.015	N	0.213	0.145	0.201204373187	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	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	0.0876	likely_benign	0.0813	benign	-0.606	Destabilizing	0.003	N	0.117	neutral	N	0.490196122	None	None	N
T/C	0.5617	ambiguous	0.4806	ambiguous	-0.298	Destabilizing	0.996	D	0.436	neutral	None	None	None	None	N
T/D	0.5029	ambiguous	0.4446	ambiguous	-0.238	Destabilizing	0.59	D	0.363	neutral	None	None	None	None	N
T/E	0.3979	ambiguous	0.3587	ambiguous	-0.289	Destabilizing	0.742	D	0.368	neutral	None	None	None	None	N
T/F	0.4769	ambiguous	0.4443	ambiguous	-0.917	Destabilizing	0.953	D	0.459	neutral	None	None	None	None	N
T/G	0.2483	likely_benign	0.2213	benign	-0.797	Destabilizing	0.59	D	0.351	neutral	None	None	None	None	N
T/H	0.3901	ambiguous	0.3258	benign	-1.161	Destabilizing	0.987	D	0.451	neutral	None	None	None	None	N
T/I	0.3499	ambiguous	0.3159	benign	-0.204	Destabilizing	0.884	D	0.397	neutral	N	0.480341552	None	None	N
T/K	0.2817	likely_benign	0.2728	benign	-0.598	Destabilizing	0.742	D	0.367	neutral	None	None	None	None	N
T/L	0.1482	likely_benign	0.1314	benign	-0.204	Destabilizing	0.742	D	0.341	neutral	None	None	None	None	N
T/M	0.1364	likely_benign	0.1121	benign	0.195	Stabilizing	0.996	D	0.419	neutral	None	None	None	None	N
T/N	0.1559	likely_benign	0.132	benign	-0.398	Destabilizing	0.015	N	0.213	neutral	N	0.485041019	None	None	N
T/P	0.1572	likely_benign	0.1283	benign	-0.307	Destabilizing	0.007	N	0.255	neutral	N	0.467027145	None	None	N
T/Q	0.3012	likely_benign	0.262	benign	-0.678	Destabilizing	0.91	D	0.43	neutral	None	None	None	None	N
T/R	0.2438	likely_benign	0.2466	benign	-0.287	Destabilizing	0.91	D	0.401	neutral	None	None	None	None	N
T/S	0.126	likely_benign	0.1104	benign	-0.625	Destabilizing	0.309	N	0.375	neutral	N	0.483771582	None	None	N
T/V	0.2017	likely_benign	0.181	benign	-0.307	Destabilizing	0.59	D	0.326	neutral	None	None	None	None	N
T/W	0.7759	likely_pathogenic	0.7417	pathogenic	-0.857	Destabilizing	0.996	D	0.595	neutral	None	None	None	None	N
T/Y	0.4574	ambiguous	0.4247	ambiguous	-0.612	Destabilizing	0.984	D	0.46	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.