TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23547	70864;70865;70866	chr2:178575493;178575492;178575491	chr2:179440220;179440219;179440218
N2AB	21906	65941;65942;65943	chr2:178575493;178575492;178575491	chr2:179440220;179440219;179440218
N2A	20979	63160;63161;63162	chr2:178575493;178575492;178575491	chr2:179440220;179440219;179440218
N2B	14482	43669;43670;43671	chr2:178575493;178575492;178575491	chr2:179440220;179440219;179440218
Novex-1	14607	44044;44045;44046	chr2:178575493;178575492;178575491	chr2:179440220;179440219;179440218
Novex-2	14674	44245;44246;44247	chr2:178575493;178575492;178575491	chr2:179440220;179440219;179440218
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-59
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.3273
• Predicted PPI site: I

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
S/T	rs1553613338	None	None	N	0.079	0.043	0.0611884634855	gnomAD-4.0.0	1.59151E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.41429E-04	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
S/A	0.129	likely_benign	0.1233	benign	-0.726	Destabilizing	0.007	N	0.207	neutral	None	None	None	None	I
S/C	0.1356	likely_benign	0.1473	benign	-0.589	Destabilizing	0.828	D	0.344	neutral	N	0.499871975	None	None	I
S/D	0.1995	likely_benign	0.2295	benign	-0.61	Destabilizing	None	N	0.048	neutral	None	None	None	None	I
S/E	0.408	ambiguous	0.4292	ambiguous	-0.624	Destabilizing	None	N	0.071	neutral	None	None	None	None	I
S/F	0.3254	likely_benign	0.3242	benign	-0.988	Destabilizing	0.356	N	0.389	neutral	None	None	None	None	I
S/G	0.0971	likely_benign	0.0967	benign	-0.949	Destabilizing	0.012	N	0.215	neutral	N	0.504437643	None	None	I
S/H	0.2137	likely_benign	0.2478	benign	-1.453	Destabilizing	0.214	N	0.373	neutral	None	None	None	None	I
S/I	0.3196	likely_benign	0.3248	benign	-0.24	Destabilizing	0.055	N	0.452	neutral	N	0.481171835	None	None	I
S/K	0.5001	ambiguous	0.5532	ambiguous	-0.735	Destabilizing	0.016	N	0.225	neutral	None	None	None	None	I
S/L	0.2066	likely_benign	0.1958	benign	-0.24	Destabilizing	0.038	N	0.332	neutral	None	None	None	None	I
S/M	0.2166	likely_benign	0.2166	benign	0.128	Stabilizing	0.628	D	0.365	neutral	None	None	None	None	I
S/N	0.0672	likely_benign	0.0728	benign	-0.708	Destabilizing	None	N	0.059	neutral	N	0.433766836	None	None	I
S/P	0.8567	likely_pathogenic	0.8661	pathogenic	-0.37	Destabilizing	0.136	N	0.393	neutral	None	None	None	None	I
S/Q	0.3733	ambiguous	0.397	ambiguous	-0.957	Destabilizing	0.072	N	0.241	neutral	None	None	None	None	I
S/R	0.5024	ambiguous	0.537	ambiguous	-0.561	Destabilizing	0.055	N	0.36	neutral	N	0.461262869	None	None	I
S/T	0.0812	likely_benign	0.0824	benign	-0.72	Destabilizing	None	N	0.079	neutral	N	0.426259287	None	None	I
S/V	0.3164	likely_benign	0.3188	benign	-0.37	Destabilizing	0.038	N	0.341	neutral	None	None	None	None	I
S/W	0.4603	ambiguous	0.4673	ambiguous	-0.946	Destabilizing	0.864	D	0.431	neutral	None	None	None	None	I
S/Y	0.1862	likely_benign	0.2053	benign	-0.676	Destabilizing	0.628	D	0.389	neutral	None	None	None	None	I

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.