TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6301	19126;19127;19128	chr2:178729137;178729136;178729135	chr2:179593864;179593863;179593862
N2AB	5984	18175;18176;18177	chr2:178729137;178729136;178729135	chr2:179593864;179593863;179593862
N2A	5057	15394;15395;15396	chr2:178729137;178729136;178729135	chr2:179593864;179593863;179593862
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: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-47
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.2976
• 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/S	rs755238352	-0.745	0.001	N	0.135	0.063	0.115124310173	gnomAD-2.1.1	4.32E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.49E-06	0
T/S	rs755238352	-0.745	0.001	N	0.135	0.063	0.115124310173	gnomAD-4.0.0	1.63359E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.92124E-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	0.0666	likely_benign	0.0658	benign	-0.984	Destabilizing	None	N	0.065	neutral	N	0.515548432	None	None	N
T/C	0.2749	likely_benign	0.2746	benign	-0.532	Destabilizing	0.356	N	0.347	neutral	None	None	None	None	N
T/D	0.2935	likely_benign	0.2612	benign	-0.123	Destabilizing	0.072	N	0.385	neutral	None	None	None	None	N
T/E	0.208	likely_benign	0.1881	benign	-0.106	Destabilizing	0.072	N	0.365	neutral	None	None	None	None	N
T/F	0.1434	likely_benign	0.1334	benign	-1.043	Destabilizing	0.072	N	0.48	neutral	None	None	None	None	N
T/G	0.2205	likely_benign	0.2102	benign	-1.258	Destabilizing	0.016	N	0.325	neutral	None	None	None	None	N
T/H	0.1745	likely_benign	0.1628	benign	-1.54	Destabilizing	0.628	D	0.415	neutral	None	None	None	None	N
T/I	0.064	likely_benign	0.063	benign	-0.336	Destabilizing	None	N	0.131	neutral	N	0.459097716	None	None	N
T/K	0.134	likely_benign	0.1232	benign	-0.686	Destabilizing	0.072	N	0.363	neutral	None	None	None	None	N
T/L	0.0725	likely_benign	0.0743	benign	-0.336	Destabilizing	None	N	0.127	neutral	None	None	None	None	N
T/M	0.0687	likely_benign	0.0659	benign	-0.03	Destabilizing	0.214	N	0.396	neutral	None	None	None	None	N
T/N	0.1084	likely_benign	0.1004	benign	-0.637	Destabilizing	0.055	N	0.323	neutral	N	0.515104118	None	None	N
T/P	0.4719	ambiguous	0.4149	ambiguous	-0.52	Destabilizing	0.106	N	0.437	neutral	N	0.497417937	None	None	N
T/Q	0.1556	likely_benign	0.1479	benign	-0.769	Destabilizing	0.356	N	0.434	neutral	None	None	None	None	N
T/R	0.1084	likely_benign	0.1002	benign	-0.527	Destabilizing	0.136	N	0.437	neutral	None	None	None	None	N
T/S	0.1005	likely_benign	0.0966	benign	-0.968	Destabilizing	0.001	N	0.135	neutral	N	0.483566416	None	None	N
T/V	0.0612	likely_benign	0.0614	benign	-0.52	Destabilizing	None	N	0.064	neutral	None	None	None	None	N
T/W	0.4671	ambiguous	0.4186	ambiguous	-0.951	Destabilizing	0.864	D	0.419	neutral	None	None	None	None	N
T/Y	0.1717	likely_benign	0.1676	benign	-0.721	Destabilizing	0.356	N	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.