Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000778542 | SCV000914834 | pathogenic | Cystinuria | 2018-10-10 | criteria provided, single submitter | clinical testing | The SLC7A9 c.671C>T (p.Ala224Val) variant has been reported in three studies in a total of nine probands with cystinuria including one in a homozygous state, three in a compound heterozygous state, and five in a heterozygous state without a second allele identified (Botzenhart et al. 2002, Rhodes et al. 2015, Halbritter et al. 2015). The p.Ala224Val variant was also found in one unaffected parent in a heterozygous state (Botzenhart et al. 2002). There is evidence that cystinuria type B can be inherited in an autosomal dominant pattern with incomplete penetrance or an autosomal recessive pattern (Barbosa et al. 2012). The p.Ala224Val variant was absent from at least 50 control samples and is reported at a frequency of 0.000071 in the European (non-Finnish) population of the Genome Aggregation Database. While cystinuria generally displays an autosomal recessive mode of inheritance, some heterozygous carriers of variants in the SLC7A9 gene have abnormal urinary amino acid patterns and an increased risk of kidney stones (Eggermann et al. 2012). Based on the evidence, the p.Ala224Val variant is classified as pathogenic for cystinuria. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Fulgent Genetics, |
RCV000778542 | SCV002799560 | likely pathogenic | Cystinuria | 2022-02-23 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002536733 | SCV003293453 | pathogenic | not provided | 2023-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 224 of the SLC7A9 protein (p.Ala224Val). This variant is present in population databases (rs140873167, gnomAD 0.007%). This missense change has been observed in individual(s) with cystinuria (PMID: 12234283, 19782624, 25109415, 25296721, 28646536, 33349102). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 631809). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC7A9 protein function. For these reasons, this variant has been classified as Pathogenic. |
| Institute of Human Genetics, |
RCV000778542 | SCV004032278 | uncertain significance | Cystinuria | 2023-08-02 | criteria provided, single submitter | clinical testing | Criteria applied: PS4_MOD,PM2_SUP,PP3 |
| Genomics England Pilot Project, |
RCV000778542 | SCV001760445 | pathogenic | Cystinuria | no assertion criteria provided | clinical testing |