Table 2.
NF1 and RNF213 rare variants identified in MMS patients.
| Patient | Sex | Genotype (cDNA and Protein Change) |
ACMG/ClinVar/LOVD Prediction |
gnomAD/ DGV Frequency |
Biogear Frequency |
|---|---|---|---|---|---|
| MMS-1 | F |
NF1 c.2536G>C (p.Ala846Pro) RNF213 c.4907C>T (p.Thr1636Met) |
P/P/P VUS/-/- |
- 2.6 × 10−5 |
- - |
| MMS-2 | M |
NF1 c.7285C>T (p.Arg2429 *) RNF213 WT |
P/P/P | - | - |
| MMS-3 | F |
NF1 c.4381delA (p.Ile1461 *) RNF213 WT |
LP/-/- | - | - |
| MMS-4 | F |
NF1 c.5483A>T (p.Asp1849Val) RNF213 WT |
P/C/VUS | - | - |
| MMS-5 | F |
NF1 c.4276_4282delinsAG (p.Gln1447Serfs * 18) RNF213 WT |
LP/-/- | - | - |
| MMS-6 | F |
NF1 c.2131delC (p.Arg711Alafs * 37) RNF213 c.10403C>T (p.Ala3468Val) |
P/P/- VUS/-/- |
- 1.3 × 10−4 |
- 7 × 10−4 |
| MMS7 | F |
NF1 c.3496+1G>A RNF213WT |
P/P/- | - | - |
| MMS-8 | F |
NF1 c.2909delA (p.Asn970Thrfs * 3) RNF213 WT |
LP/-/- | - | - |
| MMS-9 | M |
NF1 c.1399dupA (p.Thr467Hisfs * 3) RNF213 WT |
P/P/- | - | - |
| MMS-10 | M |
NF1 c.5725T>C (p.Cys1930Arg) RNF213 WT |
P/C/P | - | - |
| MMS-11 | F |
NF1 c.1642-8A>G RNF213 WT |
P/P/- | - | - |
| MMS-12 | M | NF1c.7553_7575del (exon 51 del) RNF213 WT |
LP/-/- | - | - |
| MMS-13 | F |
NF1 c5547_5943del (exons 38–39 del) RNF213 WT |
P/P/- - |
Very rare in DGV - |
- |
| MMS-14 | F |
NF1 WT ^ RNF213 c.3721G>A (p.Ala1241Thr) |
- VUS/-/- |
- 1.9 × 10−5 |
- 3 × 10−4 |
| MMS-15 | M |
NF1 c.6179T>G (p.Leu2081 *) RNF213 WT |
LP/-/- | - | - |
| MMS-16 | F |
NF1 c.2356C>A (p.Gln786Lys) RNF213 WT |
LP/VUS/- | - | - |
| MMS-17 | M |
NF1 c.610dupC (p.Leu204Profs * 12) RNF213 WT |
P/LP/- | - | - |
| MMS-18 ‡ | M |
NF1 c.586+4dupA RNF213 WT |
VUS/VUS/- | - | - |
| MMS-19 | F |
NF1 c.5010dupG (p.Tyr1671Valfs * 3) RNF213 WT |
LP/-/- | - | - |
| MMS-20 ‡ | M |
NF1 c.5767dupC (p.Ile1923Profs * 20) RNF213 WT |
P/-/- | - | - |
LOVD, Leiden open Variation Database; DGV, Database of Genomic Variants; Biogear, in-house exome controls dataset; M, male; F, female; del, deletion; VUS, variant of uncertain significance; P, pathogenic; LP, likely pathogenic; C, conflicting; WT, wild type; * stop codon; ‡, familial case; ^ The patient was not investigated by MLPA and cDNA sequencing. Reference sequences: NF1: NM_000267.3; RNF213: NM_001256071.3.