TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17000	51223;51224;51225	chr2:178611131;178611130;178611129	chr2:179475858;179475857;179475856
N2AB	15359	46300;46301;46302	chr2:178611131;178611130;178611129	chr2:179475858;179475857;179475856
N2A	14432	43519;43520;43521	chr2:178611131;178611130;178611129	chr2:179475858;179475857;179475856
N2B	7935	24028;24029;24030	chr2:178611131;178611130;178611129	chr2:179475858;179475857;179475856
Novex-1	8060	24403;24404;24405	chr2:178611131;178611130;178611129	chr2:179475858;179475857;179475856
Novex-2	8127	24604;24605;24606	chr2:178611131;178611130;178611129	chr2:179475858;179475857;179475856
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-111
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.2922
• 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
R/G	rs1488377419	None	0.81	D	0.295	0.267	0.404453528171	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/G	rs1488377419	None	0.81	D	0.295	0.267	0.404453528171	gnomAD-4.0.0	6.5799E-06	None	None	None	None	N	None	2.41278E-05	0	None	0	0	None	0	0	0	0	0
R/K	rs767481574	-0.399	0.897	N	0.271	0.195	None	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	2.81025E-04	None	0	None	0	0	0
R/K	rs767481574	-0.399	0.897	N	0.271	0.195	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.95236E-04	None	0	0	0	0	0
R/K	rs767481574	-0.399	0.897	N	0.271	0.195	None	gnomAD-4.0.0	5.14654E-05	None	None	None	None	N	None	0	0	None	0	1.83593E-03	None	0	0	8.48001E-07	0	0
R/S	None	None	0.681	N	0.289	0.175	0.231231049324	gnomAD-4.0.0	1.5932E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86202E-06	0	0
R/T	rs767481574	-0.499	0.81	D	0.307	0.451	0.453307948783	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
R/T	rs767481574	-0.499	0.81	D	0.307	0.451	0.453307948783	gnomAD-4.0.0	2.73829E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59936E-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
R/A	0.7017	likely_pathogenic	0.7704	pathogenic	-0.27	Destabilizing	0.025	N	0.133	neutral	None	None	None	None	N
R/C	0.3026	likely_benign	0.3653	ambiguous	-0.32	Destabilizing	0.999	D	0.435	neutral	None	None	None	None	N
R/D	0.7415	likely_pathogenic	0.8034	pathogenic	0.151	Stabilizing	0.965	D	0.441	neutral	None	None	None	None	N
R/E	0.5735	likely_pathogenic	0.6627	pathogenic	0.266	Stabilizing	0.965	D	0.231	neutral	None	None	None	None	N
R/F	0.7616	likely_pathogenic	0.822	pathogenic	-0.197	Destabilizing	0.98	D	0.476	neutral	None	None	None	None	N
R/G	0.495	ambiguous	0.5802	pathogenic	-0.556	Destabilizing	0.81	D	0.295	neutral	D	0.574514159	None	None	N
R/H	0.159	likely_benign	0.1922	benign	-0.966	Destabilizing	0.997	D	0.353	neutral	None	None	None	None	N
R/I	0.3771	ambiguous	0.4894	ambiguous	0.477	Stabilizing	0.838	D	0.385	neutral	D	0.616468071	None	None	N
R/K	0.2365	likely_benign	0.2038	benign	-0.267	Destabilizing	0.897	D	0.271	neutral	N	0.499602707	None	None	N
R/L	0.4434	ambiguous	0.5237	ambiguous	0.477	Stabilizing	0.739	D	0.292	neutral	None	None	None	None	N
R/M	0.5284	ambiguous	0.6414	pathogenic	-0.023	Destabilizing	0.553	D	0.162	neutral	None	None	None	None	N
R/N	0.6816	likely_pathogenic	0.756	pathogenic	0.082	Stabilizing	0.988	D	0.352	neutral	None	None	None	None	N
R/P	0.9024	likely_pathogenic	0.9143	pathogenic	0.25	Stabilizing	0.99	D	0.442	neutral	None	None	None	None	N
R/Q	0.172	likely_benign	0.2173	benign	-0.007	Destabilizing	0.965	D	0.374	neutral	None	None	None	None	N
R/S	0.7145	likely_pathogenic	0.7871	pathogenic	-0.494	Destabilizing	0.681	D	0.289	neutral	N	0.500732212	None	None	N
R/T	0.4357	ambiguous	0.5445	ambiguous	-0.206	Destabilizing	0.81	D	0.307	neutral	D	0.592675585	None	None	N
R/V	0.5559	ambiguous	0.6538	pathogenic	0.25	Stabilizing	0.072	N	0.267	neutral	None	None	None	None	N
R/W	0.3582	ambiguous	0.3994	ambiguous	-0.031	Destabilizing	0.999	D	0.457	neutral	None	None	None	None	N
R/Y	0.5303	ambiguous	0.6009	pathogenic	0.318	Stabilizing	0.997	D	0.416	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.