TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4655	14188;14189;14190	chr2:178739270;178739269;178739268	chr2:179603997;179603996;179603995
N2AB	4338	13237;13238;13239	chr2:178739270;178739269;178739268	chr2:179603997;179603996;179603995
N2A	None	None	chr2:None	chr2:None
N2B	4292	13099;13100;13101	chr2:178739270;178739269;178739268	chr2:179603997;179603996;179603995
Novex-1	4417	13474;13475;13476	chr2:178739270;178739269;178739268	chr2:179603997;179603996;179603995
Novex-2	4484	13675;13676;13677	chr2:178739270;178739269;178739268	chr2:179603997;179603996;179603995
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-29
• Domain position: 50
• Structural Position: 130
• Q(SASA): 0.3768
• 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
D/H	rs1299692717	None	0.782	D	0.429	0.359	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/H	rs1299692717	None	0.782	D	0.429	0.359	None	gnomAD-4.0.0	2.48326E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39635E-06	0	0
D/N	None	None	0.003	D	0.188	0.135	None	gnomAD-4.0.0	6.85563E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01122E-07	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
D/A	0.1502	likely_benign	0.169	benign	0.014	Stabilizing	0.338	N	0.427	neutral	D	0.575166829	None	None	N
D/C	0.5019	ambiguous	0.56	ambiguous	0.272	Stabilizing	0.991	D	0.642	neutral	None	None	None	None	N
D/E	0.1193	likely_benign	0.1424	benign	-0.188	Destabilizing	0.001	N	0.122	neutral	N	0.479760569	None	None	N
D/F	0.3711	ambiguous	0.4173	ambiguous	-0.228	Destabilizing	0.967	D	0.585	neutral	None	None	None	None	N
D/G	0.1254	likely_benign	0.1423	benign	-0.106	Destabilizing	0.338	N	0.361	neutral	D	0.587384741	None	None	N
D/H	0.1647	likely_benign	0.1879	benign	0.057	Stabilizing	0.782	D	0.429	neutral	D	0.612248467	None	None	N
D/I	0.2363	likely_benign	0.2733	benign	0.259	Stabilizing	0.906	D	0.588	neutral	None	None	None	None	N
D/K	0.1987	likely_benign	0.243	benign	0.583	Stabilizing	0.404	N	0.361	neutral	None	None	None	None	N
D/L	0.2506	likely_benign	0.292	benign	0.259	Stabilizing	0.826	D	0.57	neutral	None	None	None	None	N
D/M	0.4625	ambiguous	0.5125	ambiguous	0.315	Stabilizing	0.991	D	0.597	neutral	None	None	None	None	N
D/N	0.0852	likely_benign	0.0893	benign	0.507	Stabilizing	0.003	N	0.188	neutral	D	0.541488844	None	None	N
D/P	0.7538	likely_pathogenic	0.8238	pathogenic	0.197	Stabilizing	0.906	D	0.42	neutral	None	None	None	None	N
D/Q	0.209	likely_benign	0.2452	benign	0.484	Stabilizing	0.404	N	0.349	neutral	None	None	None	None	N
D/R	0.2355	likely_benign	0.2781	benign	0.632	Stabilizing	0.704	D	0.509	neutral	None	None	None	None	N
D/S	0.1125	likely_benign	0.1245	benign	0.394	Stabilizing	0.404	N	0.316	neutral	None	None	None	None	N
D/T	0.2062	likely_benign	0.2378	benign	0.481	Stabilizing	0.575	D	0.405	neutral	None	None	None	None	N
D/V	0.1538	likely_benign	0.1754	benign	0.197	Stabilizing	0.782	D	0.569	neutral	D	0.560630158	None	None	N
D/W	0.722	likely_pathogenic	0.7657	pathogenic	-0.224	Destabilizing	0.991	D	0.657	neutral	None	None	None	None	N
D/Y	0.1353	likely_benign	0.1471	benign	-0.01	Destabilizing	0.957	D	0.587	neutral	D	0.612376247	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.