TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4752	14479;14480;14481	chr2:178738199;178738198;178738197	chr2:179602926;179602925;179602924
N2AB	4435	13528;13529;13530	chr2:178738199;178738198;178738197	chr2:179602926;179602925;179602924
N2A	3508	10747;10748;10749	chr2:178738199;178738198;178738197	chr2:179602926;179602925;179602924
N2B	4389	13390;13391;13392	chr2:178738199;178738198;178738197	chr2:179602926;179602925;179602924
Novex-1	4514	13765;13766;13767	chr2:178738199;178738198;178738197	chr2:179602926;179602925;179602924
Novex-2	4581	13966;13967;13968	chr2:178738199;178738198;178738197	chr2:179602926;179602925;179602924
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-30
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.4796
• 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
K/E	rs1383451111	0.454	0.003	N	0.086	0.113	0.139678290688	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
K/E	rs1383451111	0.454	0.003	N	0.086	0.113	0.139678290688	gnomAD-4.0.0	7.95755E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	7.16435E-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
K/A	0.17	likely_benign	0.1983	benign	-0.197	Destabilizing	0.002	N	0.158	neutral	None	None	None	None	N
K/C	0.4947	ambiguous	0.557	ambiguous	-0.645	Destabilizing	0.497	N	0.324	neutral	None	None	None	None	N
K/D	0.1693	likely_benign	0.1971	benign	0.033	Stabilizing	0.004	N	0.172	neutral	None	None	None	None	N
K/E	0.1017	likely_benign	0.1256	benign	0.074	Stabilizing	0.003	N	0.086	neutral	N	0.413080835	None	None	N
K/F	0.5861	likely_pathogenic	0.6757	pathogenic	-0.41	Destabilizing	0.085	N	0.422	neutral	None	None	None	None	N
K/G	0.1925	likely_benign	0.2089	benign	-0.388	Destabilizing	0.004	N	0.205	neutral	None	None	None	None	N
K/H	0.1592	likely_benign	0.1708	benign	-0.461	Destabilizing	None	N	0.075	neutral	None	None	None	None	N
K/I	0.2965	likely_benign	0.3831	ambiguous	0.235	Stabilizing	0.044	N	0.401	neutral	None	None	None	None	N
K/L	0.2509	likely_benign	0.3071	benign	0.235	Stabilizing	0.004	N	0.255	neutral	None	None	None	None	N
K/M	0.1928	likely_benign	0.2306	benign	-0.219	Destabilizing	0.427	N	0.278	neutral	N	0.417498459	None	None	N
K/N	0.0947	likely_benign	0.1023	benign	-0.221	Destabilizing	None	N	0.062	neutral	N	0.375030933	None	None	N
K/P	0.3146	likely_benign	0.3741	ambiguous	0.117	Stabilizing	None	N	0.077	neutral	None	None	None	None	N
K/Q	0.0977	likely_benign	0.1108	benign	-0.259	Destabilizing	0.014	N	0.184	neutral	N	0.415858346	None	None	N
K/R	0.0704	likely_benign	0.0761	benign	-0.112	Destabilizing	0.014	N	0.161	neutral	N	0.415320593	None	None	N
K/S	0.1374	likely_benign	0.1623	benign	-0.678	Destabilizing	None	N	0.071	neutral	None	None	None	None	N
K/T	0.1052	likely_benign	0.1263	benign	-0.479	Destabilizing	None	N	0.064	neutral	N	0.415707821	None	None	N
K/V	0.2568	likely_benign	0.3172	benign	0.117	Stabilizing	0.009	N	0.225	neutral	None	None	None	None	N
K/W	0.5992	likely_pathogenic	0.6802	pathogenic	-0.472	Destabilizing	0.788	D	0.316	neutral	None	None	None	None	N
K/Y	0.3453	ambiguous	0.4036	ambiguous	-0.119	Destabilizing	0.044	N	0.403	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.