TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18278	55057;55058;55059	chr2:178602570;178602569;178602568	chr2:179467297;179467296;179467295
N2AB	16637	50134;50135;50136	chr2:178602570;178602569;178602568	chr2:179467297;179467296;179467295
N2A	15710	47353;47354;47355	chr2:178602570;178602569;178602568	chr2:179467297;179467296;179467295
N2B	9213	27862;27863;27864	chr2:178602570;178602569;178602568	chr2:179467297;179467296;179467295
Novex-1	9338	28237;28238;28239	chr2:178602570;178602569;178602568	chr2:179467297;179467296;179467295
Novex-2	9405	28438;28439;28440	chr2:178602570;178602569;178602568	chr2:179467297;179467296;179467295
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-21
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.6193
• 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
C/F	rs1213616804	-0.433	0.295	N	0.344	0.195	0.508455578974	gnomAD-4.0.0	2.16261E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.78975E-06	0	0
C/R	rs2053721931	None	None	N	0.251	0.127	0.346085882481	gnomAD-4.0.0	1.78027E-06	None	None	None	None	N	None	0	0	None	0	2.94204E-05	None	0	0	0	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
C/A	0.2333	likely_benign	0.1778	benign	-1.044	Destabilizing	None	N	0.063	neutral	None	None	None	None	N
C/D	0.4734	ambiguous	0.3529	ambiguous	-0.328	Destabilizing	0.072	N	0.397	neutral	None	None	None	None	N
C/E	0.5055	ambiguous	0.4078	ambiguous	-0.3	Destabilizing	0.038	N	0.369	neutral	None	None	None	None	N
C/F	0.1584	likely_benign	0.1159	benign	-1.009	Destabilizing	0.295	N	0.344	neutral	N	0.418701383	None	None	N
C/G	0.1682	likely_benign	0.1173	benign	-1.253	Destabilizing	0.012	N	0.285	neutral	N	0.376505257	None	None	N
C/H	0.2284	likely_benign	0.1696	benign	-1.612	Destabilizing	0.356	N	0.31	neutral	None	None	None	None	N
C/I	0.3203	likely_benign	0.2384	benign	-0.556	Destabilizing	0.038	N	0.302	neutral	None	None	None	None	N
C/K	0.3428	ambiguous	0.2731	benign	-0.261	Destabilizing	0.038	N	0.344	neutral	None	None	None	None	N
C/L	0.2405	likely_benign	0.2032	benign	-0.556	Destabilizing	0.016	N	0.326	neutral	None	None	None	None	N
C/M	0.4027	ambiguous	0.3704	ambiguous	-0.125	Destabilizing	0.356	N	0.341	neutral	None	None	None	None	N
C/N	0.2693	likely_benign	0.2147	benign	-0.128	Destabilizing	0.072	N	0.386	neutral	None	None	None	None	N
C/P	0.6218	likely_pathogenic	0.3802	ambiguous	-0.693	Destabilizing	0.136	N	0.403	neutral	None	None	None	None	N
C/Q	0.259	likely_benign	0.198	benign	-0.261	Destabilizing	0.214	N	0.399	neutral	None	None	None	None	N
C/R	0.1598	likely_benign	0.118	benign	-0.161	Destabilizing	None	N	0.251	neutral	N	0.38597289	None	None	N
C/S	0.186	likely_benign	0.132	benign	-0.506	Destabilizing	0.012	N	0.333	neutral	N	0.381201788	None	None	N
C/T	0.2837	likely_benign	0.2155	benign	-0.332	Destabilizing	None	N	0.143	neutral	None	None	None	None	N
C/V	0.2665	likely_benign	0.216	benign	-0.693	Destabilizing	0.016	N	0.278	neutral	None	None	None	None	N
C/W	0.3821	ambiguous	0.2874	benign	-1.033	Destabilizing	0.828	D	0.308	neutral	N	0.45927857	None	None	N
C/Y	0.1843	likely_benign	0.1376	benign	-0.856	Destabilizing	0.295	N	0.319	neutral	N	0.477786972	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.