TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25547	76864;76865;76866	chr2:178569493;178569492;178569491	chr2:179434220;179434219;179434218
N2AB	23906	71941;71942;71943	chr2:178569493;178569492;178569491	chr2:179434220;179434219;179434218
N2A	22979	69160;69161;69162	chr2:178569493;178569492;178569491	chr2:179434220;179434219;179434218
N2B	16482	49669;49670;49671	chr2:178569493;178569492;178569491	chr2:179434220;179434219;179434218
Novex-1	16607	50044;50045;50046	chr2:178569493;178569492;178569491	chr2:179434220;179434219;179434218
Novex-2	16674	50245;50246;50247	chr2:178569493;178569492;178569491	chr2:179434220;179434219;179434218
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-135
• Domain position: 34
• Structural Position: 51
• Q(SASA): 0.7704
• 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
V/M	rs1429730962	-0.296	0.002	N	0.248	0.037	0.0666544352282	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.66E-05	8.9E-06	0
V/M	rs1429730962	-0.296	0.002	N	0.248	0.037	0.0666544352282	gnomAD-4.0.0	6.84674E-06	None	None	None	None	N	None	0	4.47588E-05	None	0	0	None	0	0	6.29978E-06	0	1.65793E-05

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
V/A	0.0832	likely_benign	0.0862	benign	-0.518	Destabilizing	None	N	0.127	neutral	N	0.386943177	None	None	N
V/C	0.5875	likely_pathogenic	0.5863	pathogenic	-0.652	Destabilizing	0.356	N	0.399	neutral	None	None	None	None	N
V/D	0.1978	likely_benign	0.1991	benign	-0.243	Destabilizing	None	N	0.371	neutral	None	None	None	None	N
V/E	0.1469	likely_benign	0.1568	benign	-0.355	Destabilizing	0.029	N	0.48	neutral	N	0.359775218	None	None	N
V/F	0.1538	likely_benign	0.1548	benign	-0.709	Destabilizing	0.214	N	0.421	neutral	None	None	None	None	N
V/G	0.1258	likely_benign	0.1307	benign	-0.658	Destabilizing	0.012	N	0.459	neutral	N	0.402024485	None	None	N
V/H	0.3716	ambiguous	0.3722	ambiguous	-0.212	Destabilizing	0.864	D	0.469	neutral	None	None	None	None	N
V/I	0.075	likely_benign	0.0758	benign	-0.298	Destabilizing	0.016	N	0.358	neutral	None	None	None	None	N
V/K	0.1832	likely_benign	0.1988	benign	-0.45	Destabilizing	0.072	N	0.487	neutral	None	None	None	None	N
V/L	0.1107	likely_benign	0.1071	benign	-0.298	Destabilizing	0.004	N	0.298	neutral	N	0.44851171	None	None	N
V/M	0.0735	likely_benign	0.0731	benign	-0.343	Destabilizing	0.002	N	0.248	neutral	N	0.46242237	None	None	N
V/N	0.1415	likely_benign	0.1409	benign	-0.187	Destabilizing	0.12	N	0.499	neutral	None	None	None	None	N
V/P	0.3509	ambiguous	0.3778	ambiguous	-0.336	Destabilizing	0.356	N	0.475	neutral	None	None	None	None	N
V/Q	0.1676	likely_benign	0.1778	benign	-0.436	Destabilizing	0.214	N	0.471	neutral	None	None	None	None	N
V/R	0.1917	likely_benign	0.2092	benign	0.073	Stabilizing	0.214	N	0.495	neutral	None	None	None	None	N
V/S	0.1126	likely_benign	0.1132	benign	-0.573	Destabilizing	0.016	N	0.419	neutral	None	None	None	None	N
V/T	0.0865	likely_benign	0.0882	benign	-0.583	Destabilizing	0.001	N	0.205	neutral	None	None	None	None	N
V/W	0.6169	likely_pathogenic	0.6223	pathogenic	-0.779	Destabilizing	0.864	D	0.499	neutral	None	None	None	None	N
V/Y	0.3884	ambiguous	0.4079	ambiguous	-0.479	Destabilizing	0.356	N	0.409	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.