TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13856	41791;41792;41793	chr2:178636005;178636004;178636003	chr2:179500732;179500731;179500730
N2AB	12215	36868;36869;36870	chr2:178636005;178636004;178636003	chr2:179500732;179500731;179500730
N2A	11288	34087;34088;34089	chr2:178636005;178636004;178636003	chr2:179500732;179500731;179500730
N2B	4791	14596;14597;14598	chr2:178636005;178636004;178636003	chr2:179500732;179500731;179500730
Novex-1	4916	14971;14972;14973	chr2:178636005;178636004;178636003	chr2:179500732;179500731;179500730
Novex-2	4983	15172;15173;15174	chr2:178636005;178636004;178636003	chr2:179500732;179500731;179500730
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-88
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.4317
• 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
N/K	rs559906667	None	0.82	N	0.254	0.267	0.0138822411134	gnomAD-4.0.0	2.743E-06	None	None	None	None	N	None	8.9858E-05	0	None	0	0	None	0	0	0	1.16339E-05	0
N/S	rs369638798	-0.449	0.023	N	0.179	0.146	None	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
N/S	rs369638798	-0.449	0.023	N	0.179	0.146	None	gnomAD-4.0.0	1.59917E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87606E-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
N/A	0.6785	likely_pathogenic	0.6508	pathogenic	-0.046	Destabilizing	0.329	N	0.391	neutral	None	None	None	None	N
N/C	0.8365	likely_pathogenic	0.8127	pathogenic	0.04	Stabilizing	0.995	D	0.479	neutral	None	None	None	None	N
N/D	0.2888	likely_benign	0.2909	benign	-0.012	Destabilizing	0.001	N	0.045	neutral	N	0.371843967	None	None	N
N/E	0.7674	likely_pathogenic	0.7563	pathogenic	-0.08	Destabilizing	0.329	N	0.285	neutral	None	None	None	None	N
N/F	0.9029	likely_pathogenic	0.8932	pathogenic	-0.7	Destabilizing	0.944	D	0.604	neutral	None	None	None	None	N
N/G	0.5512	ambiguous	0.5164	ambiguous	-0.111	Destabilizing	0.003	N	0.09	neutral	None	None	None	None	N
N/H	0.4045	ambiguous	0.369	ambiguous	-0.132	Destabilizing	0.013	N	0.17	neutral	N	0.446551169	None	None	N
N/I	0.7889	likely_pathogenic	0.7663	pathogenic	0.026	Stabilizing	0.927	D	0.625	neutral	N	0.445346255	None	None	N
N/K	0.7509	likely_pathogenic	0.7358	pathogenic	0.04	Stabilizing	0.82	D	0.254	neutral	N	0.409563114	None	None	N
N/L	0.7623	likely_pathogenic	0.7293	pathogenic	0.026	Stabilizing	0.704	D	0.571	neutral	None	None	None	None	N
N/M	0.7586	likely_pathogenic	0.7236	pathogenic	0.003	Stabilizing	0.995	D	0.445	neutral	None	None	None	None	N
N/P	0.9602	likely_pathogenic	0.9526	pathogenic	0.023	Stabilizing	0.944	D	0.597	neutral	None	None	None	None	N
N/Q	0.7925	likely_pathogenic	0.765	pathogenic	-0.269	Destabilizing	0.828	D	0.325	neutral	None	None	None	None	N
N/R	0.8221	likely_pathogenic	0.809	pathogenic	0.11	Stabilizing	0.704	D	0.335	neutral	None	None	None	None	N
N/S	0.2866	likely_benign	0.2713	benign	-0.056	Destabilizing	0.023	N	0.179	neutral	N	0.363665098	None	None	N
N/T	0.4637	ambiguous	0.4295	ambiguous	-0.027	Destabilizing	0.473	N	0.237	neutral	N	0.339543464	None	None	N
N/V	0.7812	likely_pathogenic	0.7477	pathogenic	0.023	Stabilizing	0.704	D	0.604	neutral	None	None	None	None	N
N/W	0.9672	likely_pathogenic	0.9632	pathogenic	-0.874	Destabilizing	0.995	D	0.553	neutral	None	None	None	None	N
N/Y	0.532	ambiguous	0.4946	ambiguous	-0.536	Destabilizing	0.863	D	0.579	neutral	N	0.446551169	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.