ClinVar Miner

Submissions for variant NM_003060.4(SLC22A5):c.632A>G (p.Tyr211Cys)

gnomAD frequency: 0.00001  dbSNP: rs121908888
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186136 SCV000239161 pathogenic not provided 2023-09-19 criteria provided, single submitter clinical testing Published functional studies found cells expressing the variant showed no carnitine transport activity compared to wild-type (Frigeni et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26828774, 25087612, 23379544, 10480371, 28841266, 32778825)
Eurofins Ntd Llc (ga) RCV000186136 SCV000339309 likely pathogenic not provided 2016-02-01 criteria provided, single submitter clinical testing
Invitae RCV000006789 SCV001232818 pathogenic Renal carnitine transport defect 2023-11-17 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 211 of the SLC22A5 protein (p.Tyr211Cys). This variant is present in population databases (rs121908888, gnomAD 0.003%). This missense change has been observed in individual(s) with primary carnitine deficiency (PMID: 10480371). ClinVar contains an entry for this variant (Variation ID: 6420). 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 expected to disrupt SLC22A5 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SLC22A5 function (PMID: 28841266). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000006789 SCV002055807 likely pathogenic Renal carnitine transport defect 2021-07-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000006789 SCV002783394 likely pathogenic Renal carnitine transport defect 2021-10-21 criteria provided, single submitter clinical testing
Baylor Genetics RCV000006789 SCV004201257 pathogenic Renal carnitine transport defect 2023-10-22 criteria provided, single submitter clinical testing
OMIM RCV000006789 SCV000026985 pathogenic Renal carnitine transport defect 1999-07-01 no assertion criteria provided literature only
Counsyl RCV000006789 SCV000485512 likely pathogenic Renal carnitine transport defect 2015-12-29 no assertion criteria provided clinical testing
Natera, Inc. RCV002226443 SCV002078309 pathogenic Decreased circulating carnitine concentration 2020-12-02 no assertion criteria provided clinical testing
Natera, Inc. RCV000006789 SCV002107432 pathogenic Renal carnitine transport defect 2020-12-02 no assertion criteria provided clinical testing

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